Cannabis & Sleep

Cannabis & Sleep

We live in a very busy time with constant distractions and the capability to stay connected to one another 24/7. While this connected lifestyle has many advantages, it does not often promote healthy sleeping habits, causing many of us to fall short on both sleep duration and quality. Research on the subject indicates that nearly 50% of individuals living in the United States suffer from some form of sleep disturbance.  SYMPTOMS, CAUSES, AND PREDISPOSITIONS Sleep disturbance can come in many forms ranging from poor sleep latency due to ‘mind-chatter’, to a formal diagnosis of chronic insomnia. While severity does vary, common symptoms and risk factors associated with sleep disturbance can include: Sleep Latency Waking Frequently Waking Early Excessive Somnolence Loss of Concentration/Focus Impaired Memory  Daytime Irritability Poor Work Performance Limited Social Interactions Increased Risk of Injury Increased Risk of Developing Type 2 Diabetes Increased Risk of High Blood Pressure Increased Risk of Heart Disease Increased Risk of Mental Health Issues (Depression, Anxiety) The quality of our sleep is deeply interconnecting with nearly every other aspect of our health, and can be substantially influenced by our sleeping environment. Individuals hoping to treat sleep disturbance should begin by identifying any relevant factors and predispositions that may be contributing to a poor night’s sleep. These can include: Age (60 and over) Alcohol Consumption Anxiety Caffeine Intake Chronic Pain Depression Eating Habits (Eating Before Bed) Exercise Habits Gastro-Esophageal Reflux Disease Irregular Sleep Habits Sleep Apnea Overactive Thyroid Travel / Jet Lag  Light Pollution Medication(s) Mental Health Napping Habits Noise Pollution Screen Time / Blue Light Exposure Stress Trauma Shiftwork Early Parenthood Home Life Schedule Social Schedule TRADITIONAL TREATMENT OPTIONS Sleep disturbance is often the result of other underlying medical conditions and as such the focus of treatment should first be on these conditions. There are many traditional ways to treat sleep disturbance and improve overall sleep quality, but there is no one-size-fits-all solution and many find themselves searching for alternatives. Common treatment options for sleep disturbance can include:  MEDICATION  LIFESTYLE Melatonin: A natural sleep hormone. Sleeping Pills: Effective for short term benefits. However, effectiveness can reduce over time, and there is a potential for addiction.  Medications for Treating Primary Conditions: Sleep quality can be improved via the use of analgesics and other medications used to treat primary conditions that contribute to sleeplessness. Avoiding/Reducing Caffeine Intake Adequately Comfortable Mattress/Pillow Limiting Evening Screen Time Limiting Late Night Food Intake Maintaining Regular Night Time Routines Meditative and/or Deep Breathing Exercises Regular Exercise Stress Management CANNABIS MEDICINE TREATMENT In parts of the world where people have access to cannabis, sleep disturbance is one of the most commonly cited reasons for seeking cannabinoid treatment. Data suggests that individuals using cannabis medicine to help treat the effects of sleep disturbance also commonly report reductions in the use of traditional sleep medications. Cannabis medicine is hardly a newly discovered treatment option, as many cultures have a history of utilizing cannabis for its medicinal potentials, such as improving sleep quality. Through constant innovation and regulatory changes, today’s cannabis medicine has been carefully developed using modern cultivation methods and technologies, as well as precise product formulating to allow for a more targeted treatment approach. Due to evolving legal frameworks around the world and the creation of new product formats, cannabis medicine has steadily grown in popularity as a trusted treatment option for sleep disturbance.  Cannabinoids interact with the body’s endocannabinoid system (ECS), which helps in maintaining equilibrium within many of the different functions and systems of the human body, including the regulation of sleep cycles. Research suggests that an endocannabinoid deficiency might be an underlying factor contributing to a variety of chronic conditions, an issue that can potentially be addressed through cannabinoid treatment. Research has shown that the use of cannabis medicine is associated with significant improvements in perceived insomnia, and that delta-9-tetrahydrocannabinol (THC) and cannabinol (CBN) can have sedating effects and can decrease sleep latency. Anandamide, an endocannabinoid that shares structural similarities with THC, can affect sleep patterns. Due to the similar effects of THC and anandamide on the body, THC can be sedating at certain doses. However, there is the potential for long-term impairment of sleep quality from prolonged use of THC. Cannabidiol (CBD) has been shown to have the potential to improve REM sleep. Research also suggests that CBD may be beneficial in cases where sleep disturbance is linked to anxiety-related disorders. Additionally, CBD may be able to modulate wakefulness through activating regions of the brain involved in triggering alertness. This has potentials in improving symptoms of drowsiness and fatigue following a poor night sleep.  Research also suggests the potential for cannabis medicine to be beneficial in the treatment of conditions related to sleep disturbance. Evidences has shown that cannabis medicine can reduce symptoms of chronic pain and associated poor sleep quality. Studies also indicate that cannabinoid treatment can be beneficial for patients suffering from obstructive sleep apnea (OSA) through improved respiratory stability. Patients suffering from post traumatic stress disorder (PTSD) may also benefit from cannabis medicine through a reduction in trauma related dreams, and reduced dream recall. The overall effect of cannabis medicine on sleep can be dependent on factors such as cannabinoids used, dosage, and delivery method. Terpenes found in cannabis can also play a role in sedating potentials. Products that are dominant in the terpene myrcene have been shown to have a greater potential for sedating effects. While the current body of evidence suggests a great deal of potential benefits, additional research is still needed to fully understand the therapeutic potentials and possible side effects of cannabis medicine as a treatment for sleep disturbance, insomnia, and other chronic conditions that contribute to reduced quality and duration of sleep. To begin your cannabis medicine journey today, book an appointment now with the Savikalpa Virtual Clinic for an online doctor consultation, or request more information from a member of our highly trained clinic staff (eclinic@savikalpa.com). We pride ourselves on being one of India’s most qualified sources of fast, friendly, and professional access to ayurvedic medicine online! Interested in learning more? Send us your questions (eclinic@savikalpa.com). It is our mission to educate patients in any way we can, and we would be delighted to hear from you. Research regarding cannabis and sleep: Cannabis, Cannabinoids, and Sleep: a Review of the Literature https://link.springer.com/article/10.1007%252Fs11920-017-0775-9  The role of the CB1 receptor in the regulation of sleep https://pubmed.ncbi.nlm.nih.gov/18514375/  Endocannabinoid Signaling Regulates Sleep Stability https://pubmed.ncbi.nlm.nih.gov/27031992/ Medical cannabis use in the United States: a retrospective database study https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-020-00038-w  The effects of nabilone on sleep in fibromyalgia: results of a randomized controlled trial https://pubmed.ncbi.nlm.nih.gov/20007734/  Cannabis species and cannabinoid concentration preference among sleep-disturbed medicinal cannabis users https://pubmed.ncbi.nlm.nih.gov/26151582/  Cannabis Affects Cerebellar Volume and Sleep Differently in Men and Women https://www.frontiersin.org/articles/10.3389/fpsyt.2021.643193/full  Recent legalization of cannabis use: effects on sleep, health, and workplace safety https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5656354/ Therapeutic Uses of Cannabis on Sleep Disorders and Related Conditions https://pubmed.ncbi.nlm.nih.gov/31895189/  Cannabis, Cannabinoids, and Sleep: a Review of the Literature https://pubmed.ncbi.nlm.nih.gov/28349316/  Acute effect of vaporized Cannabis on sleep and electrocortical activity https://doi.org/10.1016/j.pbb.2019.02.012  Use of Cannabis to Relieve Pain and Promote Sleep by Customers at an Adult Use Dispensary https://doi.org/10.1080/02791072.2019.1626953  Cannabis Expectancies for Sleep https://doi.org/10.1080/02791072.2019.1643053  Cannabis, Pain, and Sleep: Lessons from Therapeutic Clinical Trials of Sativex®, a Cannabis-Based Medicine https://doi.org/10.1002/cbdv.200790150  Using cannabis to help you sleep: Heightened frequency of medical cannabis use among those with PTSD https://doi.org/10.1016/j.drugalcdep.2013.12.008  Medical Cannabis and the Treatment of Obstructive Sleep Apnea: An American Academy of Sleep Medicine Position Statement https://doi.org/10.5664/jcsm.7070  Cannabis use and sleep: Expectations, outcomes, and the role of age https://doi.org/10.1016/j.addbeh.2020.106642  Effects of Cannabis Consumption on Sleep https://link.springer.com/chapter/10.1007/978-3-030-61663-2_11  Substitution of medical cannabis for pharmaceutical agents for pain, anxiety, and sleep https://doi.org/10.1177/0269881117699616  Recent cannabis use and nightly sleep duration in adults: a population analysis of the NHANES from 2005 to 2018 https://rapm.bmj.com/content/47/2/100.abstract  Cannabidiol, a constituent of Cannabis sativa, modulates sleep in rats https://doi.org/10.1016/j.febslet.2006.04.102  Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis https://doi.org/10.1093/rheumatology/kei183  Using recreational cannabis to treat insomnia: Evidence from over-the-counter sleep aid sales in Colorado https://doi.org/10.1016/j.ctim.2019.102207  Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes https://www.liebertpub.com/doi/full/10.1089/can.2016.0009 DISCLAIMER – All individuals accessing this site undertake full responsibility for their own assessment of the accuracy/relevance of any and all content found herein. The content found on this site is not intended to serve as a substitute for medical advice/diagnosis/treatment from a qualified and licensed health care provider. This information should also in no way be misconstrued as professional legal advice regarding legislative, regulatory or any other matters. Individuals should always seek guidance of fully qualified professionals.

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Cannabis & Diabetes – What do we know, and what guidance should be given to patients with diabetes?

Cannabis & Diabetes – What do we know, and what guidance should be given to patients with diabetes?

It is always important to discuss one’s full medical history with your health care provider before beginning any new form of medical treatment or procedure. This allows your doctor to screen for any potential risk factors, complications, or side effects that are commonly linked to certain conditions.  In the case of diabetes, it is currently not common for health care providers specializing in cannabis medicine to screen for diabetes in the way they would commonly screen and/or caution patients regarding risk factors such as a history of schizophrenia or heart disease.   The relationship between cannabis medicine and diabetes is an area still requiring more extensive research. However, there has been some clinical studies on the subject to go along with a significant level of anecdotal evidence. While some of the existing data is contradictory, clinical research has been able to identify a number of potential benefits as well as reasons for diabetic patients to take extra precautions when consuming cannabis medicine products. POTENTIAL BENEFITS Despite the lack of a robust body of research regarding cannabis and diabetes, current anecdotal and clinical evidence suggests that cannabis may have either a positive or neutral effect when consumed by patients with diabetes. The endocannabinoid system (ECS) plays a role in how the body regulates food intake and body weight. Studies have shown that individuals who consume cannabis have lower rates of obesity than those who have never consumed cannabis, as well as lower rates of diabetes. Research has also shown an association between cannabis consumption and smaller waists circumferences, lower fasting insulin levels, and lower HOMA-IR. Cannabis medicine that is cannabidiol (CBD) dominant can also potentially help prevent and/or treat arterial inflammation, peripheral neuropathy, diabetic retinopathy, and gastrointestinal pain/cramping.  In jurisdictions where patients have easy access to cannabis and hemp products, it has become common for diabetic patients (relying largely on anecdotal evidence) to self-medicate using cannabinoid medicine for: Stabilizing/controlling blood sugar levels Increased insulin sensitivity Maintaining a healthy body weight Neuropathic pain relief Nerve inflammation prevention Reducing arterial inflammation Improved circulation via vasodilation Lowering blood pressure Muscle cramp relief Controlling restless leg syndrome Preventing diabetic retinopathy Limiting gastrointestinal pain/cramping Depression Improved sleep quality CANNABINOIDS AND DIABETES Studies suggest that a variety of cannabinoids found in cannabis medicine can potentially offer differing benefits and/or treatment options for patients with type 1 and type 2 diabetes. Cannabidiol (CBD)  Potential to: Reduce hyperglycemia and control blood sugar Prevent/limit inflammation Reduce neuropathic pain Decrease oxidative stress Limit vascular hyperpermeability Increase insulin production Reduce cholesterol levels Prevent diabetic retinopathy Delta-9-Tetrahydrocannabinol (THC) Potential to: Improve insulin production Relieve neuropathic pain  Reduce fasting plasma glucose Elevate adiponectin levels Delta-9-Tetrahydrocannabivarin (THC-V)  Potential to: Reduce fasting plasma glucose Increase adiponectin levels Increase apolipoprotein A levels Improve pancreatic β-cell function Significantly more clinical research is still needed to properly establish any potential benefits. However, there is enough evidence to suggest the possibility that cannabis medicine could prove to be more effective in managing diabetes than current medication commonly used for treating diabetes. REASONS TO EXERCISE ADDITIONAL CAUTION Studies have identified several risk factors regarding cannabis use and diabetes. However, these factors are most commonly associated with the recreational use of cannabis products impairing a patients’ ability for effective self-management. Those consuming a high dosage of THC resulting in feelings of euphoria or being ‘high’, may also experience an impaired ability to consistently make good choices.  This impairment can lead to: Inadequate monitoring of blood sugar and ketone levels Irregular use of prescribed medications Increased appetite High caloric intake Increased consumption of carbohydrates  Acute blood pressure increase Changes in levels of physical activity Decreased triglycerides and high-density lipoprotein cholesterol Failure to properly identify symptoms of low blood sugar  This potential for impaired self-management has been shown to double the likelihood of type 1 diabetes patients experiencing diabetic ketoacidosis (DKA). DKA is the result of excess ketone production in the body causing one’s blood to become acidic. Individuals consuming recreational cannabis and/or a regular high dosage of THC dominant cannabis products should discuss the risks of DKA with their health care provider, and increase the frequency for checking blood sugar and ketone levels.  An additional risk factor for DKA in type 1 diabetes patients is the potential for experiencing cannabinoid hyperemesis syndrome (CHS). While CHS is a rare condition linked to daily long-term consumption of high dose cannabis products, it can cause severe bouts of vomiting resulting in dehydration and increased ketone levels. Failure to properly treat DKA can result in severe dehydration, brain swelling, and even death. Beyond the potential impacts of impairment on self-management behaviours, research has also indicated a potential increased risk for: Myocardial infarction Arterial occlusion Renal disease  Additionally, the regular consumption of cannabis in young adults is linked to an increased risk of prediabetes later in life, however this is not currently linked to an increased risk of developing diabetes. CURRENT GUIDANCE Organizations such as Diabetes Canada have prepared some basic guidance based on the evidence available in order to assist doctors, educators, and social safety awareness advocates in their goals of better educating and cautioning those living with diabetes. For patients with type 2 diabetes who are able to maintain their target glucose levels and who currently practice healthy behaviors (eating right, checking levels/taking medications regularly), the primary concern is to ensure that when using cannabis products, patients are able to continue to practice good behaviors. While there is evidence that cannabis use can help in stabilizing blood sugar levels, recreational use of cannabis has been linked to diabetic patients over eating and forgetting to check their levels and/or take their medications. Thus, it is prudent to caution and educate patients on maintaining healthy habits, even if they are unlikely to experience euphoria or feel ‘high’ when using a proper dosage of a cannabis medicine product. Diabetes Canada also recommends that recreational cannabis users with type 1 diabetes should be made aware of all potential risk factors and advised to check their blood sugar and ketone levels more frequently than usual. To begin your cannabis medicine journey today, book an appointment now with the Savikalpa Virtual Clinic for an online doctor consultation, or request more information from a member of our highly trained clinic staff (eclinic@savikalpa.com). We pride ourselves on being one of India’s most qualified sources of fast, friendly, and professional access to ayurvedic medicine online! Interested in learning more? Send us your questions (eclinic@savikalpa.com). It is our mission to educate patients in any way we can, and we would be delighted to hear from you. Research regarding cannabis and Diabetes: The Role of Cannabis and Cannabinoids in Diabetes https://doi.org/10.1177%2F1474651410385860 Cannabis Use as Risk or Protection for Type 2 Diabetes: A Longitudinal Study of 18 000 Swedish Men and Women https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5098083/ Cannabis Smoking and Diabetes Mellitus: Results from Meta-Analysis with Eight Independent Replication Samples https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4801109/ Efficacy and Safety of Cannabidiol and Tetrahydrocannabivarin on Glycemic and Lipid Parameters in Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Pilot Study https://diabetesjournals.org/care/article/39/10/1777/129/Efficacy-and-Safety-of-Cannabidiol-and The Impact of Marijuana Use on Glucose, Insulin, and Insulin Resistance among US Adults https://doi.org/10.1016/j.amjmed.2013.03.002 Obesity and Cannabis Use: Results From 2 Representative National Surveys https://doi.org/10.1093/aje/kwr200 Beneficial effects of a Cannabis sativa extract treatment on diabetes-induced neuropathy and oxidative stress https://hal.archives-ouvertes.fr/hal-00483244  Randomized Placebo-Controlled Double-Blind Clinical Trial of Cannabis-Based Medicinal Product (Sativex) in Painful Diabetic Neuropathy: Depression is a major confounding factor https://doi.org/10.2337/dc09-1029 A double-blind, randomized, placebo-controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatment https://doi.org/10.1002/j.1532-2149.2013.00445.x  Neuroprotective and blood-retinal barrier-preserving effects of cannabidiol in experimental diabetes https://pubmed.ncbi.nlm.nih.gov/16400026/ Cannabis use does not impact on type 2 diabetes: A two-sample Mendelian randomization study https://doi.org/10.1111/adb.13020 Decreased prevalence of diabetes in marijuana users: cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) III https://pubmed.ncbi.nlm.nih.gov/22368296/ The effects of recreational cannabis use on glycemic outcomes and self-management behaviours in people with type 1 and type 2 diabetes: a rapid review https://systematicreviewsjournal.biomedcentral.com/articles/10.1186/s13643-020-01411-9 Cannabis Use Is Associated With Increased Risk for Diabetic Ketoacidosis in Adults With Type 1 Diabetes: Findings From the T1D Exchange Clinic Registry https://doi.org/10.2337/dc19-0365 An Unusual Cause of Recurrent Diabetic Ketoacidosis in Type 1 Diabetes https://www.amjmed.com/article/S0002-9343(16)30290-X/fulltext Marijuana use, diet, body mass index, and cardiovascular risk factors https://doi.org/10.1016/j.amjcard.2006.03.024 The relationship between cannabis use and diabetes: Results from the National Epidemiologic Survey on Alcohol and Related Conditions III https://pubmed.ncbi.nlm.nih.gov/30288813/ Marijuana Use and Type 2 Diabetes Mellitus: a Review https://pubmed.ncbi.nlm.nih.gov/27747490/ Marijuana use and risk of prediabetes and diabetes by middle adulthood: the Coronary Artery Risk Development in Young Adults (CARDIA) study https://pubmed.ncbi.nlm.nih.gov/26364621/  Cannabis use prevalence among individuals with diabetes: The National Survey on Drug Use and Health, 2005-2018 https://pubmed.ncbi.nlm.nih.gov/32470752/ Diabetes Canada Position Statement on Recreational Cannabis Use in Adults and Adolescents With Type 1 and Type 2 Diabetes https://doi.org/10.1016/j.jcjd.2019.05.010 DISCLAIMER – All individuals accessing this site undertake full responsibility for their own assessment of the accuracy/relevance of any and all content found herein. The content found on this site is not intended to serve as a substitute for medical advice/diagnosis/treatment from a qualified and licensed health care provider. This information should also in no way be misconstrued as professional legal advice regarding legislative, regulatory or any other matters. Individuals should always seek guidance of fully qualified professionals.

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Cannabis & Antibiotics

Cannabis & Antibiotics

With the use of cannabis medicine becoming more and more common around the world, one frequently asked question among patients is, can I use cannabis medicine while taking antibiotics?   Cannabis and antibiotics are currently not considered to be contraindicated. While still ongoing, the current research regarding interactions between cannabis medicine and antibiotics is somewhat limited.  Among the data that does exist, studies have suggested the following: An increased potential for experiencing side effects related to the use of antibiotics, such as vomiting, nausea, and/or diarrhea.  Antibiotics may cause a reduction in CBD levels. Clindamycin can be found on at least one doctor compiled list of potential drug interactions related to cannabis. Based on the evidence available, the consensus appears to be that the potential for interaction is low, and patients should be made aware of the increased potential for vomiting, nausea, and/or diarrhea.  The increased risk of antibiotic related side effects I likely due to the potential for cannabis to inhibit certain enzymes (cytochrome p450 enzymes) within the liver. These enzymes are involved in the biosynthesis of some antibiotics such as erythromycin, miocamycin and troleandomycin.   Should a patient begin to experience any of these negative side effects, it is recommended that they consider reducing their cannabis medicine dosage, or discontinuing their cannabis medicine treatment until the course of antibiotics is complete. When reducing or ceasing dosage, patients should also be advised that they may experience a temporary worsening of the symptoms for which they are taking cannabis, such as pain or sleep disturbance. This is necessary to prioritize the antibiotics treatment. Beyond the research in the area of drug interaction potentials, there has also been some study regarding the possible antibiotic and antimicrobial properties of cannabis.  Research is still ongoing, however thus far cannabinoids have been shown to have the following potentials: CBG has been shown to be able to kill antibiotic-resistant bacteria, including Methicillin-Resistant Staphylococcus Aureus (MRSA). CBD can kill some forms of Gram-negative bacteria, including Neisseria gonorrhoeae. CBD has the potential to enhance the effectiveness of certain antibiotics. Major cannabinoids such as THC, CBD, CBG, CBC, and CBN have all been shown to have some level of effectiveness in killings different strains of MRSA bacteria. CBD shows a low tendency to produce resistance in bacteria. This research does look promising, however it’s important to remember that further study and formulation work is needed before we can determine the efficacy and viability of any new treatment options.  To begin your cannabis medicine journey today, book an appointment now with the Savikalpa Virtual Clinic for an online doctor consultation, or request more information from a member of our highly trained clinic staff (eclinic@savikalpa.com). We pride ourselves on being one of India’s most qualified sources of fast, friendly, and professional access to ayurvedic medicine online! Interested in learning more? Send us your questions (eclinic@savikalpa.com). It is our mission to educate patients in any way we can, and we would be delighted to hear from you. Research regarding cannabis and antibiotics: A Systematic Review on the Pharmacokinetics of Cannabidiol in Humans https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275223/  An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies https://doi.org/10.1089/can.2016.0034  Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review https://doi.org/10.3109/03602532.2013.849268 A Phase I, open-label, randomized, crossover study in three parallel groups to evaluate the effect of Rifampicin, Ketoconazole, and Omeprazole on the pharmacokinetics of THC/CBD oromucosal spray in healthy volunteers https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3671111/  NTI Meds to be Closely Monitored when Co-Administered with Cannabinoids https://sites.psu.edu/cannabinoid/files/2020/06/NTI-Meds-to-be-Closely-Monitored-when-Co-Administered-with-Cannabinoids_2020_04_25.pdf Cannabis Interactions https://www.drugs.com/drug-interactions/cannabis.html  The Antimicrobial Activity of Cannabinoids https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400265/  The antimicrobial potential of cannabidiol https://pubmed.ncbi.nlm.nih.gov/33469147/  The antimicrobial effect behind Cannabis sativa https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1002/prp2.761  Cannabinoids-Promising Antimicrobial Drugs or Intoxicants with Benefits? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345649/  Antibacterial cannabinoids from Cannabis sativa: a structure-activity study https://pubmed.ncbi.nlm.nih.gov/18681481/  Uncovering the Hidden Antibiotic Potential of Cannabis https://pubmed.ncbi.nlm.nih.gov/32017534/   Cannabidiol is an effective helper compound in combination with bacitracin to kill Gram-positive bacteria https://www.nature.com/articles/s41598-020-60952-0  Antibacterial activity of delta9-tetrahydrocannabinol and cannabidiol https://pubmed.ncbi.nlm.nih.gov/1085130/  Immunoregulatory Role of Cannabinoids during Infectious Disease https://doi.org/10.1159/000481824 DISCLAIMER – All individuals accessing this site undertake full responsibility for their own assessment of the accuracy/relevance of any and all content found herein. The content found on this site is not intended to serve as a substitute for medical advice/diagnosis/treatment from a qualified and licensed health care provider. This information should also in no way be misconstrued as professional legal advice regarding legislative, regulatory or any other matters. Individuals should always seek guidance of fully qualified professionals.

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Cannabis & Drug Tolerance

Cannabis & Drug Tolerance

Drug Tolerance / Drug Insensitivity When an individual develops a diminished response to a drug following a period or repeated use. Often this is the result of prolonged use of a drug causing one’s body to adapt to the constant presence of the substance. Classes of Drug Tolerance Dynamic Tolerance: Adaptive changes to receptor sites in the brain. Dispositional Tolerance: Changes in how a drug is absorbed by the body. Behavioral Tolerance: Administration environment familiarity. It is not uncommon for individuals over time to develop tolerance to a medication, resulting in a drop in the effectiveness of symptom management from their prescribed dosage. This can occur through a change in how the body metabolizes a drug, or in the case of cannabis medicine, changes in cell receptors within the body (CB1 receptors). Common medications that are associated with drug tolerance/insensitivity also include: Opioids Antidepressants Antibiotics Anxiolytics Chemotherapy drugs In the case of cannabis medicine, tolerance is most commonly associated with patients who are consuming doses with a high potency of delta-9-tetrahydrocannabinol (THC) over an extended period of time. Tolerance can also be affected by one’s gender, DNA, pervious use history, and drug delivery method. Cannabis tolerance is caused by the downregulation of the body’s CB1 receptors. The regular presence of THC in the body can inhibit CB1 receptor sensitivity, and reduce the number of CB1 receptor sites available for binding through receptor internalization. In the short term, patients can benefit from an increased tolerance to THC through a reduction in potential unwanted side effects such as intoxication or psychomotor impairment. However, over time this tolerance can also lead to a limiting of the sedative and pain-relieving effects of THC. Additionally, prolonged use of THC dominant cannabis medicine can potentially also result in increased synthesis of pregnenolone in the brain. Increased levels of this hormone might ultimately result in limiting the effects of THC by acting as a signal inhibitor for the CB1 receptor. Mitigating Cannabis Drug Tolerance When discussing medical cannabis and drug tolerance, it is important to note that this downregulation of the body’s CB1 receptors is associated with THC consumption and not cannabidiol (CBD). Current research suggests that the consumption of CBD does not result in CB1 downregulation or an increase in drug tolerance. Thus, if a patient is able to achieve sufficient symptom management from CBD without the use of THC, they might be able to avoid or limit the effects of tolerance. The effects of cannabis tolerance can also be mitigated through the use of a dosage schedule that incorporates a gradual increase in dosage potency. By increasing dosage gradually, patients will be able to better maintain their experienced levels of symptom relief. However, as dosage potency increases, so does the rate of tolerance, thus regardless of how carefully one schedules their treatment regimen, they will eventually experience reduced effectiveness in symptom management. The most effective method for reducing tolerance and regaining the full symptom relief potentials of cannabis medicine, is through taking scheduled tolerance breaks (also known as ‘t-breaks’). Once a patient reaches the point where increasing their dosage to achieve greater efficacy is no longer deemed practical and/or safe, they should talk to their doctor about a tolerance break. When a patient ceases their course of cannabis treatment for a tolerance break, research suggests that the replenishment of CB1 receptor availability can begin within the first 48 hours. Some in the medical cannabis community recommend that patients who rely on cannabis for the treatment of chronic conditions should consider taking a two day break once every 30 days, in order to limit the effects of tolerance. For those who’s condition/symptom severity will allow for longer breaks, research indicates that after a break of two weeks, experienced effects should begin returning to normal. In four weeks, CB1 receptor function/density is observed to return to near normal. After taking a tolerance break, patients should be aware that they might now be more susceptible to the intoxicating effects of THC than they were prior to taking this break. Patients should thus consider starting again at a lower dosage, both to avoid unwanted effects, and to gauge the possible therapeutic potentials of a lower dose. Cessation and the Potential for Withdrawal Symptoms Anecdotally, patients reporting that they have experienced withdrawal symptoms after stopping a course of cannabis treatment is generally uncommon, and usually involves symptoms of low to moderate severity. However, various studies on the subject have reported the rate of patients who experience some form of withdrawal symptoms as being anywhere from 35% to 75%, with a noted potential for greater symptom severity to be experienced by women. Patients who report experiencing withdrawal symptoms typically begin experiencing symptoms between 24-72 hours following cessation. With peak symptoms being experienced after seven days. Mild symptoms can potentially persist for as many as four weeks. The associated symptoms of cannabis withdrawal and their limited severity are sometimes likened to those commonly associated with caffeine withdrawal. Potential symptoms can include: Sudden return and/or increased severity of symptoms being managed Reduced Appetite Upset Stomach and/or Nausea Sleep Disturbance Vivid Dreams Irritability Mood Swings Restlessness Fatigue Headaches Loss of Focus Depression Dysphoria Patients are recommended to help manage withdrawal symptoms by staying well hydrated, getting plenty of bed rest, and engaging in regular exercise to achieve a natural boost in one’s mood. Over-the-counter remedies can be useful in managing symptoms of nausea and headache. There is also some evidence to suggest that CBD can potentially help in alleviating symptoms of withdrawal. Weaning of Dosage Prior to Cessation In light of the evidence suggesting that there is a possibility of experiencing some form of withdrawal symptoms, it would be prudent for patients to speak with their doctor about a gradual weaning of one’s dosage prior to ending a course of treatment or beginning a tolerance break. This should be considered if frequently consuming a high THC dosage and/or an extended duration of treatment. While the gradual weaning off of cannabis medicine is far less common than immediate cessation, there is the possibility that it may help further reduce the potential for experiencing withdrawal symptoms. For those wishing to limit the possibility of experiencing these symptoms through weaning, patients should gradually decrease the THC potency of their dosage as well as dosage frequency over the course of approximately ten days. Dosage should also be limited to the evenings while weaning, in order to best limit potential symptoms of sleep disturbance. EXAMPLE WEANING CHART: Original Dosage DAY 1 DAY 2 DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 DAY 8 DAY 9 DAY 10 Potency (THC) 10mg 10mg 7.5mg 7.5mg 5mg N/A 5mg N/A 2.5mg N/A 2.5mg Frequency x 2 Morning /Evening x 1 Evening Only x 1 x 1 x 1 N/A x 1 N/A x 1 N/A x 1 To begin your cannabis medicine journey today, book an appointment now at the Savikalpa Virtual Clinic for an online doctor consultation, or request more information from a member of our highly trained clinic staff (eclinic@savikalpa.com). We pride ourselves on being one of India’s most qualified sources of fast, friendly, and professional access to cannabis medicine online! Interested in learning more? Send us your questions (eclinic@savikalpa.com). It is our mission to educate patients in any way we can, and we would be delighted to hear from you. Research regarding cannabis and drug tolerance: Cannabis use and the development of tolerance: a systematic review of human evidence https://www.sciencedirect.com/science/article/abs/pii/S0149763418302665 Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers https://www.nature.com/articles/mp201182 Rapid Changes in CB1 Receptor Availability in Cannabis Dependent Males after Abstinence from Cannabis https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4742341/ Rapid CB1 cannabinoid receptor desensitization defines the time course of ERK1/2 MAP kinase signaling https://www.sciencedirect.com/science/article/abs/pii/S0028390807001712 Blunted highs: Pharmacodynamic and behavioral models of cannabis tolerance https://www.sciencedirect.com/science/article/abs/pii/S0924977X20300225 Time course for the induction and maintenance of tolerance to Delta(9)-tetrahydrocannabinol in mice https://pubmed.ncbi.nlm.nih.gov/10940538/ Regional enhancement of cannabinoid CB1 receptor desensitization in female adolescent rats following repeated Δ9-tetrahydrocannabinol exposure https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2962820/ Regulation of CB1 cannabinoid receptor internalization by a promiscuous phosphorylation-dependent mechanism https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3707135/ Aspects of tolerance to and dependence on cannabis https://pubmed.ncbi.nlm.nih.gov/828472/ Clinical relevance of cannabis tolerance and dependence https://pubmed.ncbi.nlm.nih.gov/6271820/ Cannabidiol regulates behavioural alterations and gene expression changes induced by spontaneous cannabinoid withdrawal https://pubmed.ncbi.nlm.nih.gov/29624642/ Prevalence of Cannabis Withdrawal Symptoms Among People With Regular or Dependent Use of Cannabinoids https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146100/ The Grass Might Be Greener: Medical Marijuana Patients Exhibit Altered Brain Activity and Improved Executive Function after 3 Months of Treatment https://www.frontiersin.org/articles/10.3389/fphar.2017.00983/full The cannabis withdrawal syndrome: current insights https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5414724/ Sex differences in cannabis withdrawal symptoms among treatment-seeking cannabis users https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747417/ DISCLAIMER – All individuals accessing this site undertake full responsibility for their own assessment of the accuracy/relevance of any and all content found herein. The content found on this site is not intended to serve as a substitute for medical advice/diagnosis/treatment from a qualified and licensed health care provider. This information should also in no way be misconstrued as professional legal advice regarding legislative, regulatory or any other matters. Individuals should always seek guidance of fully qualified professionals.

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Why cannabis can make your heart race

Why cannabis can make your heart race

One of the most common unwanted side effects of cannabis, a spike in heart rate, also happens to be one of the most troublesome and can even turn new users off from the plant. “If you don’t explain that it’s possible that you can have a little acceleration of the heart for maybe 5 or 10 minutes and that it’s nothing to worry about,” said Janosch Kratz, MD, on The Cannabis Enigma podcast, “he gets nervous and says, ‘oh God, why did I take this drug.'” For a healthy individual cannabis-induced tachycardia is usually harmless, and knowing more about what cannabis is doing to your body can make you feel better about the unpleasant feeling. So why can cannabis raise your heart rate? Is it dangerous? And what can you do about it? Let’s find out.  How cannabis affects your heart in general Cannabis has a number of common side effects, ranging from mild ones such as red eyes, dry mouth, or the munchies, to potentially more unpleasant effects such as anxiety, paranoia, and short-term memory difficulties.  These side effects, and how cannabis affects the cardiovascular system, are related to how it modulates what is known as the endocannabinoid system. The endocannabinoid system affects a wide range of bodily functions including hunger, pain, sleep, and energy, to name a few.   The major active chemicals in cannabis — cannabinoids — are able to trigger receptors that control the endocannabinoid system, modifying the function of those receptors and the connected systems, including the cardiovascular system.   “The interactions of the endocannabinoid system with the autonomic nervous system seem to be the driving force behind the reported cardiovascular adverse events [from cannabis],” wrote a group of researchers who recently reviewed years of cannabis studies1.  Why cannabis makes your heart race  An increased or irregular heart rate, also known as tachycardia, can be a side effect of cannabis use. In fact, smoking cannabis can lead to a 20-100% increase in heart rate for a couple hours or more after consumption2. This is believed to be due to a widening of the blood vessels, which is also responsible for those red eyes people get after using cannabis.  In higher doses cannabis can also lead to a drop in blood pressure, resulting in dizziness and lightheadedness. The main culprit for these effects of cannabis is widely-considered to be tetrahydrocannabinol (THC), the cannabinoid also responsible for the high of marijuana.  One of the more oft-cited, albeit dated reports states that inhaling cannabis smoke and ingesting THC reliably increases the heart rate by 20-50% over baseline. A lab study carried out on rodents in 1985 further showed that THC significantly alters the levels of catecholamine — hormones that are produced by the adrenal glands and are responsible for the body’s “fight or flight” response — in the bloodstream. Research has also shown that as one’s tolerance to cannabis increases, the severity of side effects often decreases3. This means that side effects commonly seen with inhaled cannabis, including increased heart rate and reduced blood pressure, is not as common in regular users. It should be noted that almost all studies on the risks of cannabis use are based on people who inhaled marijuana smoke, and that with more and more people now preferring other methods and types of cannabis, these risk assessments should be updated. In other words, like with some other cannabis side effects, the effect on heart rate can be partly attributed to the act of smoking itself4.  Could lower THC strains affect your heart rate less? Since THC is often cited as being responsible for the increased heart rate after cannabis use, one might logically conclude that choosing lower-THC strains — or lower doses in general — would help mitigate it. It would also follow that eating edibles high in THC could produce the same side effects.  Dr. Deepak Cyril D’Souza, a professor of psychiatry at the Yale University of Medicine told NBC news in November, 2020 that he has spent 25 years studying the effects of marijuana and THC and that “in our studies on THC, we found a very robust increase in heart rate and an effect on blood pressure that can be quite profound.” A 1988 trial found that women given very low-THC (1.8%) joints showed “statically significant increases in pulse rate,” and this increase was more pronounced and lasted longer for participants with a past history of intermittent marijuana use5. The trial did not include a control population given a lower dose of THC however.  The most well-known and common strains (more correctly referred to as “chemovars”), high in THC and low in cannabidiol (CBD) and often bred for a strong high and medicinal benefits, are increasingly referred to as Type I cannabis. Type II chemovars have more of a balance between CBD and THC, while Type III chemovars are CBD dominant with little-to-no THC.  All types of cannabis can be used therapeutically, but types II and III tend to allow for better control of THC doses and are often preferred by healthcare professionals due to the reduced risk of side effects. Type III cannabis, despite containing small amounts of THC, is generally considered non-intoxicating. What about CBD?  It is increasingly accepted that CBD, which doesn’t cause an intoxicating effect, can counteract some of the effects of THC6. This happens because CBD can actually modify THC binding with certain receptors of the endocannabinoid system. In other words, using a strain that has less THC or more of a CBD-dominant profile, should — by virtue of containing less THC — produce a less powerful high, and may reduce the anxiety that can commonly accompany a THC high. As far as the effects CBD itself has on the heart, a 2017 trial found that a single dose of CBD reduced resting blood pressure and helped mitigate stress-induced blood pressure and heart-rate increases7.  A 2013 comprehensive published in Frontiers in Psychology looked at CBD’s ability to offset the “adverse psychological effects of THC,” and concluded that “the few studies that exist on the effects of CBD show that this cannabinoid can counteract some of the negative effects of THC.”  Is sativa or indica worse for your heart rate? It’s conventional wisdom in cannabis that sativa strains are upbeat and indica strains are mellow and likely to induce the “couch lock” sensation. Countless cannabis consumers use these characterizations to shape their consumption or purchasing decisions Unfortunately, there isn’t much scientific evidence to support this notion of indica vs sativa as a method of distinguishing between the effects of different types of cannabis. While there are many factors at play in determining why a cannabis chemovar produces certain effects, calling them indica or sativa is not one.  What does matter is the cannabinoid profile of the chemovar (how much THC, CBD, and other cannabinoids) and its terpene makeup. The various terpenes in cannabis not only determine its flavor and aroma, but may also have a big impact on its effects, including how energetic or sedative the high is.  Also, it’s worth keeping in mind that this can be very individualistic. The right dose for one individual can be very different than the right dose for another person, and a strain that makes one person very upbeat and giggly could induce a couch-lock sensation for someone else. And while a specific strain may be very relaxing to one person, another user could experience anxiety or paranoia, but this would not indicate that this is a universally-experienced effect of the cannabis variety in question. The same could be true for increased heart rate. Is cannabis dangerous for the heart?  View this post on Instagram A post shared by Savikalpa Academy (@savikalpa.academy)   If you are a young, healthy person with no history of cardiac illness, then you probably should not be overly concerned about the cardiovascular side effects of cannabis use.  A 2018 review of existing research into marijuana use and cardiovascular risk factors found that there is “insufficient” evidence about how marijuana affects cardiovascular risk factors including stroke and heart attack8. The researchers stated that the current literature on the matter is limited by “recall bias, inadequate exposure assessment, minimal marijuana exposure, and a predominance of low-risk cohorts.” That doesn’t mean that there may not be cause for concern. In fact, there is a substantial amount of data to suggest cannabis may increase the risk of cardiac disease Researchers in 2014 examined the reporting of cardiovascular complications related to cannabis use and found that they “indicate cannabis as a possible risk factor for cardiovascular disease in young adults.”9 More recently, a 2017 review discussed “harmful effects of cannabis use including fatal cardiovascular events that could be related to cannabis use,” including but not limited to increased heart rate and blood pressure and a heightened risk of acute coronary events10.  Cardiac-related mortality data from the U.S. National Vital Statistics System for 1990-2014 and showed a statistically significant increase of 2.4% in the rate of cardiac death among men following the passage of medical cannabis programs, as well as 1.3% increase among women11.  Other research has found that cannabis use is associated with an increased risk of cardiac dysrhythmia12, as well as non-fatal stroke, transient ischemic attack13, and acute myocardial infarction14. Importantly, cannabis users are more likely to be using tobacco products than non-cannabis users, which may contribute to these negative cardiac outcomes. In general, if you are considering using cannabis, you may want to speak to your physician about the possible side effects, especially if you have a history of cardiovascular issues. Can you do anything about increased heart rate from cannabis? When it comes to cardiovascular health and cannabis, many of the same healthy lifestyle principles apply: Try to limit or cut out smoking as an intake method, exercise regularly, eat healthy, and try to get a full night’s sleep as often as possible.  If you find that you often get anxiety or your mind (along with your heart) races when you get high, then consider trying a lower-THC variety, or one that has more of an even balance between THC and CBD. This will help keep your THC dose lower and reduce the likelihood of a racing heart and racing mind. And when those intense feelings strike, use some tried and true ways to bring your high down a little bit. First off, don’t panic. Remember that the high will wear off before too long, and this isn’t a permanent condition. Try to focus on your breathing, taking deep breaths to help you relax and bring your anxiety down. You can also try to find something funny on the TV, put on an album you love listening to, and when in doubt, raid the cupboard for snacks. Sources Latif, Z., & Garg, N. (2020). The Impact of Marijuana on the Cardiovascular System: A Review of the Most Common Cardiovascular Events Associated with Marijuana Use. Journal of clinical medicine, 9(6), 1925. https://doi.org/10.3390/jcm9061925 Goyal, H., Awad, H. H., & Ghali, J. K. (2017). Role of cannabis in cardiovascular disorders. Journal of thoracic disease, 9(7), 2079–2092. https://doi.org/10.21037/jtd.2017.06.104 Jones R. T. (2002). Cardiovascular system effects of marijuana. Journal of clinical pharmacology, 42(S1), 58S–63S. https://doi.org/10.1002/j.1552-4604.2002.tb06004.x Subramaniam, V. N., Menezes, A. R., DeSchutter, A., & Lavie, C. J. (2019). The Cardiovascular Effects of Marijuana: Are the Potential Adverse Effects Worth the High?. Missouri medicine, 116(2), 146–153. Lex, B. W., Mendelson, J. H., Bavli, S., Harvey, K., & Mello, N. K. (1984). Effects of acute marijuana smoking on pulse rate and mood states in women. Psychopharmacology, 84(2), 178–187. https://doi.org/10.1007/BF00427443 Laprairie, R. B., Bagher, A. M., Kelly, M. E., & Denovan-Wright, E. M. (2015). Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor. British journal of pharmacology, 172(20), 4790–4805. https://doi.org/10.1111/bph.13250 Jadoon, K. A., Tan, G. D., & O’Sullivan, S. E. (2017). A single dose of cannabidiol reduces blood pressure in healthy volunteers in a randomized crossover study. JCI insight, 2(12), e93760. https://doi.org/10.1172/jci.insight.93760 Ravi, D., Ghasemiesfe, M., Korenstein, D., Cascino, T., & Keyhani, S. (2018). Associations Between Marijuana Use and Cardiovascular Risk Factors and Outcomes: A Systematic Review. Annals of internal medicine, 168(3), 187–194. https://doi.org/10.7326/M17-1548 Jouanjus, E., Lapeyre-Mestre, M., Micallef, J., & French Association of the Regional Abuse and Dependence Monitoring Centres (CEIP-A) Working Group on Cannabis Complications* (2014). Cannabis use: signal of increasing risk of serious cardiovascular disorders. Journal of the American Heart Association, 3(2), e000638. https://doi.org/10.1161/JAHA.113.000638 Goyal, H., Awad, H. H., & Ghali, J. K. (2017). Role of cannabis in cardiovascular disorders. Journal of thoracic disease, 9(7), 2079–2092. https://doi.org/10.21037/jtd.2017.06.104 Latif, Z., & Garg, N. (2020). The Impact of Marijuana on the Cardiovascular System: A Review of the Most Common Cardiovascular Events Associated with Marijuana Use. Journal of clinical medicine, 9(6), 1925. https://doi.org/10.3390/jcm9061925 Hemachandra, D., McKetin, R., Cherbuin, N., & Anstey, K. J. (2016). Heavy cannabis users at elevated risk of stroke: evidence from a general population survey. Australian and New Zealand journal of public health, 40(3), 226–230. https://doi.org/10.1111/1753-6405.12477 Hemachandra, D., McKetin, R., Cherbuin, N., & Anstey, K. J. (2016). Heavy cannabis users at elevated risk of stroke: evidence from a general population survey. Australian and New Zealand journal of public health, 40(3), 226–230. https://doi.org/10.1111/1753-6405.12477 Mittleman, M. A., Lewis, R. A., Maclure, M., Sherwood, J. B., & Muller, J. E. (2001). Triggering myocardial infarction by marijuana. Circulation, 103(23), 2805–2809. https://doi.org/10.1161/01.cir.103.23.2805   This article was originally published on The Cannigma, and shared here with permission.

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What is the entourage effect?

What is the entourage effect?

The entourage effect is a hypothesis that was first suggested in the early 2000s, based on the notion that consuming a whole plant may be more effective than taking an isolated medication that is based only on one of a plant’s active compounds.  The hypothesis has been developed a lot since it was first posited. Today, some scientists believe different types of cannabis can be more or less effective for specific conditions and symptoms — and also the type of high they can cause — based on their chemical profiles.   What is the entourage effect? Most prescription drugs are based on a single molecule. There are even two FDA-approved drugs based on the two main molecules in cannabis — the cannabinoids THC and CBD. Cannabis, however, is a plant containing hundreds of compounds.  In 1999, researchers Shimon Ben Shabat and Raphael Mechoulam first mentioned that, as a plant, cannabis may be superior to some pharmaceuticals thanks to the effect of entourage compounds. This hypothesis was based on their observations when researching the endocannabinoid system, however, not the cannabis plant.  They observed that some endocannabinoids naturally produced in the body are more effective when delivered with other, non-active compounds. Or in their words, “Biologically active natural products… are in many instances accompanied by chemically related, though biologically inactive, constituents… Investigations of the effect of the active component in the presence of its ‘entourage’ compounds may lead to results that differ from those observed with the active component only.”  They concluded that “this type of synergism may play a role in the widely held (but not experimentally based) view that in some cases plants are better drugs than the natural products isolated from them.”  A couple of years later, researcher Elizabeth Williamson provided evidence for the concept that “a whole or partially purified extract of a plant offers advantages over a single isolated ingredient.”1  One of the examples used was the ability of CBD to attenuate some of THC’s side effects. She concluded that “this synergistic effect will become very important if cannabis becomes a medicine by reducing the often undesirable psychotropic side effects.”    How does the entourage effect work?  Though a number of researchers have contributed to the entourage effect theory as it relates to cannabis, the name most associated with it is Dr. Ethan Russo. In his 2011 paper, “Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects,” Russo thoroughly presented the previous works on cannabinoid synergy, basically coined the term “entourage effect,” and defined its mechanism.2 To explain how the entourage effect works, Dr. Russo cited a 2009 study from Germany that defined the way herbal synergy works in general, not just in cannabis. It described four main mechanisms, three of which are particularly relevant for cannabis:3 Multi-target enhancing effects Most often, drugs operate on one or two molecular targets in our bodies, creating a specific effect. A multi-target effect means plant compounds can operate on many targets. In cannabis, a popular example would be the interaction of THC with CB1, CB2, GPR18, GPR55, TRPV2, TRPV3, and many other receptors. This multitude of targets can potentiate the effects of THC.But it’s not just about THC — there are other cannabinoids, terpenes, and maybe even flavonoids that can also potentially activate a multitude of targets, thereby enhancing or modulating the effects of THC. One of the earliest published examples of the potentiating effects of THC when administered in a synergistic manner, was the comparison of a pure THC medication with a whole plant extraction in the treatment of spasticity. With equal doses of THC, a whole plant extraction was deemed “considerably more effective antispastically than THC alone.”4 Molecular movement enhancing effects The two main branches of pharmacology are pharmacodynamics (how drugs affect your body) and pharmacokinetics (how your body affects drugs, or the movement of drugs within the body). While the multi-target enhancing effects of cannabis are associated with the former, the movement enhancing effects of cannabis are related to pharmacokinetics.  The result is similar (an enhanced effect of THC or CBD), but the way there is a bit different. The multi-target enhancing effect is caused by the interaction of molecules on a variety of targets. While the movement enhancing effects of whole-plant cannabis is caused by the way a group of molecules (an entourage) travels in the body in a more efficient manner than if one of them travels alone.  One example of molecular movement enhancing effects is exemplified by the terpenes limonene and pinene. These terpenes are biologically active,5,6 and can cause relaxation of the lungs and airway, but when taken may not themselves produce a major bodily response (at least not at safe doses). But when terpenes are inhaled along with cannabinoids, the absorption of cannabinoids through the lungs could be improved by the presence of these bronchodilating terpenes.  Modulation of adverse effects These effects “can be reached when a constituent contained in a plant extract…’neutralizes’ or destroys a toxicaly acting constituent and, therefore, generates a better effectiveness as compared with the original raw drug.”7Several adverse effects of cannabis are associated with THC, and though there are a few cannabis compounds that may help counteract these adverse effects, the best and most popular is CBD.There is a growing amount of research supporting the ability of CBD to attenuate THC adverse effects, particularly impaired memory8, anxiety9, and psychotomimetic effects (such as paranoia and social withdrawal)10.  Terpenes and cannabinoids – the entourage effect in cannabis In “Taming THC,” Dr. Russo also added a new research direction: Maybe it’s not just the interaction of THC and CBD but also other cannabis compounds — such as minor cannabinoids, terpenes, and flavonoids — that play a role in the entourage effect. Terpenes are aromatic molecules responsible for the smell and taste in most plants, but they are also pharmacologically active and can influence the body. One of the unique things about cannabis is its terpene content variability (there are almost 200 different terpenes in cannabis).  According to Dr. Russo, the abundant terpenes in a given chemovar are likely to determine its effects. Those terpenes may influence whether it’ll be sedating or stimulating, and whether it will be better for conditions and symptoms such as pain, inflammation, anxiety, epilepsy, or depression.  Some examples of potential cannabinoid-terpenoid synergy suggested in “Taming THC” include:  THC + pinene = Bronchodilator THC + limonene, pinene or linalool = Beneficial in Alzehimer THC + linalool and/or myrcene = Muscle relaxant CBD + linalool and/or limonene = Anxiolytic CBD + linalool = Anticonvulsant CBD + limonene = Immunostimulant CBD + pinene = Anti-inflammatory THC and/or CBD + linalool = Analgesic  Though there’s some evidence for cannabinoid synergy (mainly THC and CBD), the terpenoid-cannabinoid synergy, as logical as it may be, is  only supported by little evidence for now. But this may be due to lack of research on the matter.   How to take advantage of the entourage effect There are a few ways to practically use this information, but before we dive into that, it’s important to note that terpenoid-cannabinoid synergies are mostly based on preliminary research. While it does make a lot of sense, there isn’t a lot of concrete evidence to support whether it can work on humans. The most important rule when it comes to the entourage effect is to seek out cannabis flowers or whole-plant products over isolates. Then, there are a number of actions you can take to optimize your experience, or when choosing the right strain for you.  Define an objective. What are you trying to achieve with cannabis? Have a relaxing evening, better focus when working, treat seizures, relieve pain? Investigate. Learn about the cannabinoids and terpenes that have been shown to be potentially useful for what you’re trying to achieve. Explore. Look for chemovars high in these cannabinoids and terpenes. Test. Conduct some trial and error until you find the chemovar that fits you.  Cannabis research still has a long way to go. For now, there’s no way to suggest a specific cannabis product for a given condition or use. But you can use the information we do have to narrow down the possibilities.  What if I don’t have access to the chemical profile?  If you live in a place with no legal cannabis program, or if your neighborhood dispensary doesn’t provide more information than the THC and CBD content of their products, you may still have other ways to sprinkle some entourage in your weed.  Let’s say you’d like to have two main chemovars in your life, one for a good night’s sleep, and another that’s more energizing and focusing for daytime. According to the entourage effect, pinene could help with memory and focus, while beta-caryophyllene (BCP) and linalool may help with insomnia.  All you need to do is infuse your cannabis with some extra pinene for your daytime chemovars, and BCP or linalool for your nighttime chemovar. There are a few ways in which you can do that, and they all involve other plants or their essential oils. However, keep in mind that these methods are based on logic rather than scientific literature.  Also, as described earlier, terpenes aren’t unique to cannabis — they can be found all over nature. In fact, while the variability of different terpenes in cannabis is unique, the total terpene content in cannabis is rather poor compared to other plants, and usually ranges between 1-3.5%.11 In comparison, the essential oil of lavender may consist of more than 85% terpenes12. Here are some ways to get some more terpenes in your weed: 1) Add in botanicals Get some dry lavender flowers and add them to your nighttime chemovar before you smoke or vape it. The high concentration of linalool from the lavender could synergize with the THC and CBD in your weed. For your daytime chemovar, you can add some dry rosemary leaves, which are often high in pinene that may help with memory and concentration. Be sure to use dried, clean herbs if trying this and be aware that a little goes a long way. 2) Buy it infused Get some terpene infused rolling papers, these can increase the terpene content of whatever you’re inhaling. Different brands offer infused papers and suggest the potential effects they may create. For instance, uplifting, relaxing and joyful.  3) Set the aroma or mood Try to guide your cannabis experience with external terpenes by diffusing essential oils while you enjoy your cannabis. Get a diffuser, close the doors and windows, and diffuse a few drops of essential oils (rosemary or sage, for instance, are high in pinene). Once the odors of the essential oil starts kicking in, take a few deep breaths and enjoy the scent, then proceed to smoking or vaping your weed. For night time, you can use the essential oil of clove or cinnamon for some BCP, or an essential oil of lavender or sage for some linalool.  4) Infuse the herbs Here you can use either dry herbs or essential oils, though the latter may work better as they have higher concentration of terpenes. When putting your cannabis flowers in a container (preferably made of glass), if you add another source of terpenes, the flower within the container will absorb some of the added terpenes from the air in the jar. To infuse your weed with herbs,  add some dry rosemary, lavender, or clove to your jar of cannabis or place a few drops of essential oils on some cotton balls and leave them in the jar with the cannabis flowers so they can absorb the terpenes.  If you are using essential oils, make sure to use quality products from reputable brands such as doTERRA or Neal’s Yard, as this is an unregulated market that often offers low quality products with questionable ingredients. How the entourage may change the industry Assuming that the entourage effect is true, and cannabinoids and terpenes can synergize and play a role in how different types of cannabis influence the body, there may be some practical implications for cannabis researchers, consumers, health care professionals, growers, and manufacturers. What the entourage effect means for consumers  One of the main implications of the entourage effect for consumers will be the way they choose cannabis products. If the cannabinoid and terpenoid profiles of cannabis plants determine their effects, we will need a system to categorize and group these products.In an ideal world, after a lot of research is done on the entourage effect, cannabis products could be grouped for uses and treatments best suited for conditions and symptoms such as pain, sleep, nausea, headaches, and seizures. They could also be distinguished as daytime or nighttime evening products, better suited for a slow evening, partying, or working.  In any case, the current strain names or indica/sativa nomenclature won’t cut it when it comes to chemical profiles. They only refer to morphological differences at best, and often completely ignore the chemical profiles of cannabis products. What the entourage effect means for research  Two of the main limitations of cannabis research are a lack of funding and conflicting results. Both are related to the entourage effect.   Conventional therapies usually use drugs that are based on one or two molecules that bind to one or a few receptors. The entourage effect intrinsically defies that approach. It suggests an herbal synergy in cannabis, in which multiple compounds target multiple targets.This encourages a paradigm shift: Should researchers distinguish between cannabis chemotypes or chemovars? Chemotypes are either high in THC or CBD (or they can have a 1:1 ratio). Chemovars, on the other hand, look past the CBD:THC ratio, and are defined by the exact concentrations of cannabinoids, and their most abundant terpenes.Moving forward with chemovars, while using the preliminary research suggested by the entourage effect may help lead researchers to more accurate results. At the moment there may be different studies that investigate how cannabis can help with a given condition or symptom. But sometimes researchers are using entirely different formulations — sometimes just THC, sometimes a mixture of THC and CBD, or even a whole plant extraction.  According to the entourage effect hypothesis, comparing the results of many of these studies is flawed because they often test different treatments altogether.  If the hypothesis is accurate, then future studies should use a more precise chemovar-driven approach to researching cannabis. It could provide health care professionals with valuable insights into therapy, and provide consumers clearer guidance on expected effects of a particular product.  The only problem is that cannabis is a plant, and patenting a plant is no picnic. There is very little incentive to fund expensive clinical trials with specific chemovars — a return on investment comparable to pharmaceutical drugs is unlikely. In addition, the illegality of cannabis has prohibited and effectively banned university-based research that often occurs in emerging fields like cannabinoid science, which is why many of the questions raised by the entourage effect remain unanswered. What the entourage effect means for cultivation and production The entourage effect may also affect cannabis cultivation, as it will need to evolve to meet the future demands of the market. Nowadays most chemovars are just high in THC with varying terpenes, but mostly high in myrcene or beta-caryophyllene.  If consumers start seeking out cannabis with more diverse chemical profiles in order to take better advantage of the entourage effect, there will most likely be an increase in demand for varying concentrations of THC and CBD and other minor cannabinoids, but also of a larger variety of terpenes.  On the production side, there will be a need for a more elaborative labeling, one that presents more than just the THC and CBD concentrations, but also other cannabinoids and terpenes. This could happen — and in some places is already happening — either because consumers are demanding to know more, or because of regulations that mandate it. Criticism  More than 20 years have passed since the first mention of a potential entourage effect in cannabis, but not all scientists agree with the hypothesis. In fact, some openly cast doubt on it.  In a recent article in the journal, “Expert Review of Clinical Pharmacology,” Peter Cogan argued that there is a lack of sufficient scientific evidence to support the entourage effect, that it’s often presented as an established clinical phenomenon as opposed to an hypothesis, and pointed to the vast misuse of that information by marketers in order to promote their cannabis products.13 Indeed, some of this criticism is valid. When the entourage effect was first suggested, it was proposed as an hypothesis — an observed phenomenon that needs to be further investigated. Nevertheless, cannabis companies, particularly CBD ones, use it in their promotional content to promote their whole plant based products as healthier and more efficient.  The lack of evidence, on the other hand, may reflect more on the lack of research rather than on the lack of entourage. In addition, the review ignores some of the more concrete clinical evidence for herbal synergy in cannabis, some of which was presented above.  Other recent studies that looked for evidence of a terpenoid-cannabinoid entourage couldn’t find evidence for such activity. They were preclinical studies that didn’t involve human subjects, however. 14, 15 On the other hand, another recent study does provide early evidence of a cannabis entourage effect. Researchers from the University of Arizona found that terpenes such as alpha humulene, linalool, and beta pinene can boost cannabinoid activity. Furthermore, the researchers wrote, they “are multifunctional cannabimimetic ligands,” or molecules that mimic cannabinoids, “that provide conceptual support for the entourage effect hypothesis and could be used to enhance the therapeutic properties of cannabinoids.”16 There’s a growing number of countries and states that legalize medical use of cannabis, even though they already have access to CBD and THC pharmaceutical drugs. And there is some scientific evidence17 and a lot of anecdotal reports showing that both THC and CBD pharmaceutical preparations are more likely to cause side effects than whole plant preparation with equivalent amounts of either THC or CBD.  Herbal synergy in cannabis likely does exist, and it could help explain the variable effects of cannabis. However, there’s a lot of hype and marketing around the entourage effect but very limited scientific evidence to support the theory.  Sources https://pubmed.ncbi.nlm.nih.gov/11695885/ Russo E. B. (2011). Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. British journal of pharmacology, 163(7), 1344–1364. https://doi.org/10.1111/j.1476-5381.2011.01238.x Wagner, H., & Ulrich-Merzenich, G. (2009). Synergy research: approaching a new generation of phytopharmaceuticals. Phytomedicine : international journal of phytotherapy and phytopharmacology, 16(2-3), 97–110. https://doi.org/10.1016/j.phymed.2008.12.018 https://pubmed.ncbi.nlm.nih.gov/19211237/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524888/ https://pubmed.ncbi.nlm.nih.gov/26456328/ https://pubmed.ncbi.nlm.nih.gov/19211237/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5435777/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604171/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5719112/ https://pubmed.ncbi.nlm.nih.gov/29161743/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767019/ https://pubmed.ncbi.nlm.nih.gov/32116073/ https://doi.org/10.1089/can.2019.0016 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6757239/ https://www.nature.com/articles/s41598-021-87740-8 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334252/   This article was originally published on The Cannigma, and shared here with permission.

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What is microdosing cannabis and why do it

What is microdosing cannabis and why do it

The medical benefits of cannabis (and its active ingredients like THC and CBD) are hard to deny. So if cannabis is working well for your medical conditions, you might think that the more cannabis you take the better it will work at relieving your symptoms. But is this true? In the midst of a cannabis market with increasingly potent cannabis options, some are choosing a different route. Instead of increasing their cannabis intake they are scaling it back with something called “microdosing.” What is Microdosing?  Microdosing is the practice of taking a much smaller dose of a medication than is normally used. It’s a practice used with all kinds of compounds, but most often discussed with psychoactive substances such as LSD. Recently people have started to apply the practice to cannabis and its popular ingredients, THC and CBD. View this post on Instagram A post shared by Savikalpa Academy (@savikalpa.academy) One recent clinical trial found that microdosing just 1 mg of THC, and even 0.5 mg, was effective at relieving chronic pain. One reason for microdosing cannabis is that taking a small amount may help to access it’s helpful effects without engaging negative side effects like a psychoactive high. But microdosing cannabis is also helpful for those who are trying to avoid triggering the wrong side of something called a biphasic effect.  To explain this simply, when a substance (like THC) has a biphasic effect, it means that it can produce two opposing effects — depending on the dose of the substance taken. Consider, for example, alcohol, which at low doses might make someone feel a bit energized, happy and chatty — but at high doses might leave them sedated, depressed and antisocial.  For many substances, these biphasic effects are important because the dose taken can drastically impact the effect it has on the human body. And with cannabis, multiple biphasic effects have been noted.  Cannabis’ Biphasic Effects Cannabis’ two most common and popular ingredients, THC and CBD, have been noted to have a variety of biphasic effects. One of the most commonly reported biphasic effects from cannabis is THC’s effect on anxiety. While many report cannabis can help ease their anxiety, others say that it makes them more anxious and paranoid. The science supports these claims, showing that dosing can make a big impact on how cannabis and its components affect anxiety. Studies on both animals and humans have found that while lower doses of THC tend to relieve anxiety, higher doses can spike it.  For example, in one animal study, mice given low doses of THC spent more time in open areas than controls (an indication of reduced anxiety), while those given high doses of THC spent less time in these stressful spaces (suggesting increased anxiety).  In one human study, a group of 42 patients were given a placebo, a low dose of THC (7.5mg), or a high dose of THC (12.5mg). Then they were subjected to various stress inducing tests and asked to rate their stress. Those in the low THC group showed reduced stress during these tests, but those who had the higher dose were more likely to have increased stress.   In another human study, a group of incarcerated patients with PTSD were given even lower doses (4mg) of the synthetic cannabinoid Nabilone, which mimics THC’s effects. Researchers found this low dose resulted in significant improvement in PTSD associated insomnia, nightmares, general symptoms, and even chronic pain. Still despite success treating anxiety conditions at these lower doses, the average dosing for cannabis products is around 10mg — which might be too high for some. And it’s not just anxiety that can benefit from microdosing. Biphasic effects from THC have been noted for pain, temperature regulation, motivational processing, appetite, novelty seeking, and locomotion and exploration. Biphasic responses have also been found for CBD with effects like pain, sedation, nausea and vomiting relief, and immune responses.  For many of cannabis’ effects — a lower dose might be the most effective option.  How to Microdose Cannabis Microdosing can be very helpful for some, and the research on biphasic effects suggests it could be particularly helpful for patients dealing with pain, appetite, energy or mood related issues like anxiety and depression. As we’ve seen above, all of these issues are common reasons for cannabis use that have strong dose-dependant biphasic reactions. So microdosing can be a great way to hone in on an optimal dose.  With microdosing, patients are advised to use the smallest dose that they can, which might be a small puff with an inhaled method like smoking or vaping, or a dose around 2.5mg for edibles or sublingual options.  There are few downsides to microdosing cannabis (when compared to taking larger doses) in terms of risk factors, but for some microdosing might not be the best option. Some patients actually do need a larger dose to effectively manage their condition. Take for example, studies on migraines, which show that relief is usually achieved only after high doses (around 20mg). Still, in the process of finding the optimal dose, starting with microdosing can be helpful. By starting low, patients can slowly increase their dosing to find an optimal dose. As they go up, they may find that the symptoms they are treating improve. But at a certain point, if they continue to increase, they are likely to hit a dose where the cannabis is actually causing negative symptoms. If this happens, they can return to the last dose that relieved their symptoms. For some, a microdose may actually be the most effective option. This is important because there can be big differences in how individuals respond to cannabis. In addition to condition related differences in the cannabis needed, there are also differences in how sensitive individuals are to the effects of cannabis because of genetic differences and differences in previous cannabis experience (which can make you tolerant to its effects). So an optimal dose for one patient might be 2mg while for another patient it might be more like 20mg. Either way, if you aren’t sure what your optimal dose is, starting low and slowly increasing is the best way to find out.  If you think microdosing cannabis might be right for you, talk with a practitioner who specializes in cannabinoid medicine. They can help make sure you are on the right track before you begin or change any cannabis regimen.    This article was originally published on The Cannigma, and shared here with permission.

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What is CBG?

What is CBG?

CBG (cannabigerol) is by far one of the most important cannabinoids in the cannabis plant. It is often called “the mother of all cannabinoids,” and it holds potential as a treatment for conditions such as diabetes, ALS, and Huntington’s disease, although human studies are seriously lacking. In addition to its potential medical applications, much like CBD, CBG is not considered intoxicating and will not get you high.  Many of the more popular and well-known effects of THC and CBD are derived from their interaction with the endocannabinoid system. CBG, however, mainly works through other mechanisms, which explains why it has such different effects. It is currently being researched as a treatment for a long list of conditions, such as dementia, PTSD, ADHD, Huntington’s disease, ALS, Parkinson’s disease, multiple sclerosis, diabetes, colitis, and of course, pain.  But it’s important to note that when it comes to CBG the word “potential” is of essence. Most of the evidence scientists have found regarding the efficacy of CBG is based on animal models, so it’s too early to say whether they are relevant for humans. And unlike THC and CBD, there’s practically no scientific information about the safety or dosing of CBG-dominant products.  Why is CBG so popular?  First isolated by Rephael Mechulam and Yehiel Gaoni in 1964, CBG is often referred to as “the mother of all cannabinoids,” suggesting that it is superior to other cannabinoids.  One of the reasons marketers often refer to CBG as “the mother of all cannabinoids” is to make it seem as if it is responsible for the benefits of the other cannabinoids, but at this time there is little science to suggest that.  What the “mother of all cannabinoids” really means is that CBGA is produced first by the plant, then is converted to other cannabinoid acids. So really, CBGA is responsible for the creation of THCA, CBDA, and CBCA because the plant needs CBGA to make them. This is important for scientists researching the plant, but does not mean it is superior therapeutically.  In fact, CBG usually occurs in much lower concentrations than other cannabinoids like THC and CBD — typically around 0-1% in a cannabis flower. With the hype surrounding CBG in the past few years, however, breeders have been developing CBG-dominant varieties, and companies are producing a multitude of products such as CBG oils and flowers.  It is important to note that research on the safety of CBG dominant products is remarkably scarce. It is possible that much of the hype about CBG is the result of a regulatory loophole that makes hemp-derived products accessible and legal. CBD has been a huge success in the wellness market, and though CBG is often proposed as its heir, there isn’t much to it yet from a scientific perspective. CBG vs CBD  Which is better, CBG or CBD? The answer depends on what you’re trying to achieve. CBG binds to different receptors that can produce a variety of effects in the body. For some conditions, like hypertension, CBG shows potential benefits that CBD doesn’t. In other cases, like controlling seizures, CBD is helpful while CBG isn’t. Still for other symptoms, like inflammation and pain, both CBD and CBG work on the same targets and can have similar effects. It really depends on what you’re trying to achieve. Unlike CBD, however, research on the safety and efficacy of CBG is practically non-existent. CBD products are often sold as dietary supplements due to a regulatory loophole, but CBD — albeit far from being fully understood — has been heavily studied for its safety and efficacy in a variety of symptoms and conditions. CBG products are accessible through the same regulatory loophole, but there’s not enough research to assess the safety and efficacy of CBG dominant products, especially when it comes to drug interactions.  How does CBG work? Unlike THC, which primarily interacts with the receptors of the endocannabinoid system, CBG produces most of its effects by binding to other families of receptors such as TRPs and the PPARs. This is important because it is one of the reasons CBG can produce such different effects than THC. Some of the receptors CBG interacts with are of interest for treating neurodegenerative and metabolic conditions, but others could actually cause drug interactions with medications that treat conditions like depression. The research on how CBG works is still ongoing and is fairly complex, but here’s a simplified review of what science knows.  CBG and the PPARs The PPARs (short for Peroxisome Proliferator-Activated Receptors) are a group of receptors with three main types  — PPAR alpha, gamma, and delta. PPAR-gamma plays a crucial role in the functioning of the nervous system and is also involved in the mechanisms of conditions such as diabetes and obesity. In fact, pharmaceutical companies have produced medications designed to treat diabetes (type II) that work on this receptor, but the drugs have been associated with serious side effects. CBG is suggested to be an agonist (activator) of PPAR-gamma, which may explain its potential role in treating neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and its potential for treating metabolic diseases like diabetes and high cholesterol.  CBG and the alpha-2 adrenoceptor  CBG is a potent agonist (activator) of alpha-2-adrenoceptor, which means it could potentially have utility as an anti-hypertensive, sedative, and analgesic. It could also play a potential role in improving impaired prefrontal cortex functioning, which is relevant for conditions such as ADHD, tic disorders, PTSD, and dementia. While all of this is exciting, it’s important to note that researchers’ understanding of this mechanism is still very limited, and CBG has not formally been tested for any of these conditions. All existing research on CBG is preliminary and based exclusively on animal models or lab studies done in test tubes. It is not yet clear to scientists exactly how CBG interacts with the three different types alpha-2 adrenoceptors, known as subtypes. As a consequence, the effectiveness of CBG for these conditions remains unknown. In addition, it is not known if CBG produces adverse effects related to the alpha-2 receptors such as changes in blood pressure, sedation, or interactions with other cardiovascular medications. How CBG works with TRP receptors  The TRPs (Transient Receptor Potential) are a large and diverse family of receptors that are usually involved in sensing and feeling changes in temperature. TRPs can interact with phytocannabinoids like THC and CBD, and other plant chemicals like capsaicin and menthol. The importance of these receptors are still being studied, but CBG can activate some of them to various degrees (TRPV1, 2, 3, and 4 and TRPA1) and block others (TRPM8). Some of the activities are similar to the way CBD interacts with these receptors, and may explain how CBG could potentially help with chronic pain, inflammation, and skin health.  CBG’s interaction with serotonin You may have heard of serotonin, an important neurotransmitter that plays a role in regulating functions such as mood, happiness, sleep, and hunger. Serotonin is particularly well known for the role it plays in conditions like depression and the group of SSRI (selective serotonin reuptake inhibitor) medications that influence it. One of many receptors serotonin binds to is 5-HT1a, with which many endocannabinoids and phytocannabinoids like CBD and CBG also interact. CBG is a potent antagonist (blocker) of 5-HT1a, which means it could easily alter the effects of other psychiatric medications.  However, the way CBG influences serotonin hasn’t been properly studied. Some researchers fear the potential dangerous consequences of high-CBG products being available to the public before its drug interactions and effects are better understood. How CBG works on cannabinoid receptors CBG can bind to the two main cannabinoid receptors (CB1 and CB2), but this interaction seems to be somewhat weak and produce complex pharmacological effects. GPR-55, a receptor that is increasingly being called a “potential CB3 receptor,” but currently there’s no knowledge about the activity of CBG on that receptor. The benefits of CBG CBG presents a rich pharmacological profile that could potentially have a lot of benefits for neurodegenerative conditions like Huntigton’s disease, ALS, Parkinson’s disease, and MS. It may also be of great benefit in inflammatory conditions like colitis, and also for metabolic conditions like diabetes and obesity. Once again, it’s extremely important to note that CBG research is still in its infancy and is very limited. Scientific evidence of its efficacy and safety in humans is practically non-existent. The best way to use the following information is when trying to find the right strain for you. If CBG shows potential for the condition you’re treating, it may make sense to prioritize cannabis products with some CBG. However, unless prescribed by a health care professional that specializes in cannabis therapy, you should avoid using CBG-dominant products such as CBG oil in order to avoid potential contraindications and drug interactions.  The potential of CBG as a neuroprotector CBG is currently being studied as a potential treatment for neurodegenerative conditions such as Huntington’s disease, ALS, Parkinson’s disease and multiple sclerosis. Scientists believe the neuroprotective properties of CBG (but also CBD) are mediated mainly through their interaction with the PPARγ receptor (which is not technically part of the endocannabinoid system). CBG and Huntington’s diseaseResearch on CBG as a treatment for Huntington’s disease shows it could be beneficial in preventing striatal neuron death (one of the main symptoms of Huntington’s disease), reducing inflammation, and improving motor activity. Some studies were more promising than others, and even more important — the studies were done in cell cultures or in animal models and have yet to be examined on humans. CBG and ALSIn a 2018 study, a derivative of CBG (called VCE-003.2) was able to improve neuropathological symptoms, and delay the progression of ALS in mice. Applicability in humans is still unclear, but PPAR-gamma and antioxidant effects were thought to be responsible. CBG and Parkinson’s diseaseUsing the same CBG derivative, the authors of another 2018 study were able to reduce three types of inflammation associated with Parkinson disease in mice. Again, this study was in mice and it’s unclear if this translates to humans. CBG and MS (multiple sclerosis)A 2012 study that looked at the potential of a CBG derivative in the treatment of Multiple Sclerosis concluded that it could potentially treat MS related inflammation in the central nervous system and help restore motor function impairment. Once again it is thought that CBG does this by reducing inflammation and preventing cellular damage as an antioxidant, but for now we only know that it’s effective in mice. CBG could help with gastrointestinal disease CBG and colitisA 2013 study on CBG for inflammatory bowel diseases concluded that “CBG may represent a new therapeutic opportunity in IBD.” The researchers suggested that CBG could be effective in preventing and treating colitis. A 2020 study examined the efficacy of CBG vs CBD for treating colitis in mice, finding that CBG was effective but CBD was not. The scientists then compared CBG and fish oil, CBD and fish oil, or all three together, and found that CBG combined with fish oil was more effective than CBD and fish oil, and that all three together were the most effective.  CBG and chemotherapy associated weight loss and loss of appetiteThere are studies showing CBG can increase appetite and reduce weight loss associated with chemotherapy, although in an earlier study CBG didn’t demonstrate any impact on appetite. So the jury is still out when it comes to appetite and CBG. One of the reasons this is an interesting research direction is because unlike THC, which is being looked at as a therapy to help with weight loss, CBG won’t get you high. CBG for diabetes and hypertension Diabetes and hypertension play a leading role in metabolic syndrome, a condition that affects up to one-third of adult Americans. Metabolic syndrome is described as a combination of elevated glucose, obesity, hypertension, and high cholesterol, and CBG shows signs as a potential treatment for both insulin resistance and hypertension. Although the evidence is preliminary, it seems to be very promising.  HypertensionCBG is currently the only cannabinoid known to activate alpha-2 receptors, which could mean that it has a role in treating high blood pressure.   Insulin resistanceA 2020 study showed that CBG, and the combination of CBG and CBD, could potentially increase insulin sensitivity. This makes sense given that CBG is an activator PPAR-gamma and there are already FDA approved drugs with this same mechanism for treating diabetes. How to use CBG There is great potential for CBG’s therapeutic uses, but science has a long way to go before we’ll have reliable information on how and when to use CBG products. Whether it is CBG oil, CBG cannabis flower, or any other CBG-dominant product, you should be cautious. Particular caution should be used if you take prescription medications, as CBG’s potential drug interactions, dosing recommendations, and contraindications are still being investigated.  Many marijuana chemovars on the market today have varying levels of CBG. If you already have a cannabis regimen for one of the conditions that could be helped by CBG (Huntington’s disease, ALS, Parkinson’s disease, MS, etc ) it would make sense to seek out products or strains that have at least some CBG. However, unless you’ve consulted a healthcare professional with cannabis expertise, you should probably avoid products in which CBG is the primary active ingredient. With the potential to treat a lot of incurable and burdensome conditions, cannabigerol is indeed one of the most interesting cannabinoids out there. However, for now the research is still too limited for good guidance surrounding its use. Until its safety and efficacy are more properly understood, you may want to wait before jumping on the CBG bandwagon.   This article was originally published on The Cannigma, and shared here with permission.

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Is 2-AG the most important endocannabinoid?

Is 2-AG the most important endocannabinoid?

If you’re familiar with endocannabinoids, it’s likely you’ve heard of the most well known one—anandamide (AEA or N-arachidonoylethanolamine). This notorious endocannabinoid has a name that means “bliss molecule” and is known for its involvement in pleasure and reward processes within the brain.  There’s another endocannabinoid that doesn’t get as much attention, but it’s equally as important as AEA and can be hundreds of times more abundant in the brain. It goes by the name of 2-arachidonoylglycerol (2-AG).1 Like most of the endocannabinoid system (ECS), the discovery of 2-AG can be traced back to Israeli scientist Dr. Raphael Mechoulam. He and his PhD student Dr. Ben-Shabat first isolated 2-AG from the intestines of canines in 19952. They also identified that 2-AG has THC-like properties in mice, thus establishing 2-AG’s place within the ECS. Similar to anandamide, 2-AG is essential to maintaining homeostasis (balance) in the body. It does this in many complex ways, but similar to THC and anandamide, most of 2-AG’s actions are mediated through actions at the CB1 and CB2 receptors. Its abundance suggests that 2-AG is one of the most important endocannabinoids, regulating numerous important processes throughout the body. These processes include a number of important physiologic functions3 including: regulating hunger mediating inflammation moderating mood reducing pain 2-AG and food intake Anyone who has ever experienced the munchies can attest that the ECS has a well-established role in moderating food intake. In fact, numerous animal studies have shown a significant relationship between 2-AG levels, hunger and metabolism.  Researchers have found that 2-AG levels in certain parts of the brain are increased during fasting, where it is responsible for mediating the feeling of hunger and the compulsion to eat. Once fed, the 2-AG levels in parts of the brain decrease back to normal.4 It’s not hard to see how a dysregulated ECS could lead to problems with appetite and metabolism. 2-AG is an important part of a balanced ECS, and when it is pushed out of balance, there can be significant consequences. In the case of food intake, too much 2-AG could lead to excessive hunger, and too little could lead to a lack of appetite. Some scientists speculate that 2-AG is a contributing factor to the global obesity problem. Overconsumption of omega-6 fats, like those from corn or canola oil, may be leading to an ECS imbalance for much of the modern world. Because 2-AG is made from omega-6 fats, overconsuming them may be leading to increases in appetite via the ECS, contributing to a vicious cycle of gaining weight and overeating.5 These speculations, like much of our knowledge of cannabis, are based primarily on rodent studies and have yet to be confirmed by human clinical investigations. 2-AG and nervous system inflammation Scientists have found in recent years that diseases of the nervous system often have an inflammatory component, which means treatments may have therapeutic benefits. Cannabinoids have been shown to have anti-inflammatory properties6 and may be helpful in treating some neurodegenerative diseases. Furthermore, scientists are very interested in how the ECS, and 2-AG specifically, is involved in the development of certain neurologic diseases. Neurodegenerative diseases like Huntington’s disease, Parkinson’s disease, and Alzheimer’s disease are very burdensome, and finding an effective treatment for these diseases is a priority for scientists. Animal models have shown that by manipulating the levels of 2-AG, by turning on or off the enzymes responsible for its production and degradation, scientists may be able to improve clinical outcomes.7 It’s true that 2-AG itself has anti-inflammatory actions within the brain, especially by interacting with CB1 and CB2 receptors. However, that isn’t the only role it plays in the inflammatory pathway. 2-AG has now been found to serve as a reserve of an important fatty acid in the body called arachidonic acid (AA). Common anti-inflammatory medications like ibuprofen(Advil), naproxen(Aleve), and acetaminophen(Tylenol) all target parts of the AA cascade.  The problem is that AA serves as the precursor for both pro-inflammatory and anti-inflammatory signaling in the body. In other words, 2-AG serves as one mediator in a complex system and its role is not one dimensional–it can be both pro-inflammatory and anti-inflammatory.8 2-AG and anxiety  Everyone experiences anxiety from time to time, but when that feeling becomes too intense or too frequent, it may become intrusive and develop into generalized anxiety disorder. It is not yet clear what exactly the role of 2-AG in anxiety is, but there is no doubt that it is involved. Generally speaking, 2-AG appears to reduce anxiety. However, the ECS is not that simple of a system. If 2-AG levels remain elevated for an extended period of time, down-regulation of CB1 and CB2 receptors could occur, which could induce changes to baseline mood and anxiety.9 This is likely due to the CB1 receptor playing a major role in regulating anxious and depressive behaviors. 2-AG also plays a major role in mediating the stress hormone known as cortisol. When under stress, be it physical, mental or emotional stress, the body releases hormones to help protect itself. Scientists have figured out that 2-AG levels follow closely behind rising cortisol levels during times of stress.10 It’s not entirely clear why the body releases 2-AG along with cortisol, but a leading theory is that while stress signalling is important, too much of it is a bad thing. The body releases 2-AG at the same time as cortisol to help create balance, sending the signal back to the brain to turn off the cortisol. 2-AG and depression Stress is one of the main causes of depression, and 2-AG is intimately and complexly involved with the stress response. Therefore 2-AG and depression have a relationship that is connected through the stress response. As per usual, the ECS plays a homeostatic role, helping to regulate the release of stress hormones like cortisol.11 There are numerous animal models showing abnormal 2-AG levels associated with depression. It is not yet clear if these abnormalities are the cause or symptom of the depression. In either case, animal studies have also found that numerous antidepressants can alter 2-AG levels in certain parts of the brain, suggesting that actions within ECS may be responsible for their antidepressant effects.12 Leveraging the endocannabinoid system for the treatment of depression makes sense, because the ECS has a well-established role in neuroplasticity and neurogenesis. 2-AG, through complex cellular mechanisms, can mediate the adaptability of the brain and body. In other words, the ECS helps humans respond to the world around them, helping them master a new skill, and new language, or a new movement. The nervous system is a dynamic system and the ECS helps to keep it agile and able to adjust to the changes of life. Modifying 2-AG levels could be helpful to those having difficulty adjusting to stress, thereby reducing symptoms of depression. 2-AG and addiction Given 2-AG’s broad actions in the brain noted above and AEA’s involvement in pleasure and reward processes, it comes as little surprise that this endocannabinoid plays a critical role in mediating reward and addiction. In the case of ethanol, drinking appears to cause a release of 2-AG which eventually leads to a release of dopamine, the reward chemical in the brain. Early rodent studies suggest that in the brain, reducing the amount of 2-AG that is produced reduces alcohol consumption.13 It isn’t just alcohol, though. Endocannabinoid levels (both 2-AG and anandamide) have been found to be altered by numerous addictive substances including nicotine, THC, ethanol, and opioids.14 Modifying levels of 2-AG may be beneficial to those who struggle with substance use disorders. Similar to anandamide, 2-AG is a pain mediator. Numerous studies manipulating 2-AG levels have shown it plays an important role in all types of pain, especially inflammatory pain. It has been shown that local administration of 2-AG causes pain-relieving effects. In all the studies that found 2-AG benefited pain, it was a diminishing effect. 2-AG plays an important role in pain signaling and pain desensitization, and it does so by interacting directly or indirectly with receptors CB1, CB2, and/or TRPV1 in numerous parts of the body.15 Through this two-fold mechanism, 2-AG is a critical regulator of both inflammatory and neuropathic pain. 2-AG vs AEA vs THC When you look at the full name of the endocannabinoids, you can see they are quite similar: N-arachidonoylethanolamine (anandamide)   VS   2-arachidonoylglycerol (2-AG).  But those small name changes correlate to significant molecular changes and different functions within the body. That’s what really sets 2-AG apart from anandamide; the actions at the receptor site in the body. You see, each endocannabinoid is a unique key that opens the lock (aka the receptor) in a specific way.  In the case of anandamide and THC, they act remarkably similar in the body and open the lock similarly—they are both known as partial agonists (activators) at CB1 and CB2 receptors. If you think of activating the receptor like turning on a light bulb, THC and AEA both act similar to a dimmer switch, where the light is only partially turned on. This is different from 2-AG, which is considered a full agonist at both of these receptors which would be the equivalent of turning the light fully on.16 This means 2-AG produces a more robust biological response than partial agonists like anandamide.  This type of agonist can be useful, but regular exposure to full agonists can increase the risk of adverse effects and can also lead to tolerance development. This difference in agonism is very important pharmacologically and is one of the biggest distinguishing factors between 2-AG and anandamide. There are numerous other nuances between these endocannabinoids, with one of the most important being affinity. Anandamide is very strongly attracted to the CB1 receptors, whereas 2-AG is not nearly as compelled to engage with CB1. Another primary difference is general abundance in the body. 2-AG can be found at significantly higher levels than anandamide within most tissues throughout the body.  The difference in affinity means that, despite being much more abundant throughout the body, anandamide can out-compete 2-AG at the CB1 receptor site. This type of endocannabinoid competition could help to explain the complex and dynamic actions of the ECS. If 2-AG is so important, why haven’t you heard of it? Well, it’s unclear why 2-AG  has not been talked about as much about anandamide. Perhaps it’s because anandamide was discovered first. Perhaps it’s the name—2-AG can’t compete with a name like “bliss molecule.” It is also possible that because anandamide functions almost exactly like THC in the body, people feel drawn towards it. In any case, 2-AG plays a crucial role throughout the body and brain and it shouldn’t be overlooked. How can you increase/decrease 2-AG levels?  Some food can contain 2-AG; in particular, milk may contain significant amounts.17 But chugging a bunch of milk would not be a good way to directly increase your 2-AG levels, as most of it would be broken by the body before it can be absorbed. It is also unclear how pasteurization, a mandatory process for most milk sold in stores, would affect the endocannabinoids present in milk. Some natural products may also contain molecules that can modify endocannabinoid breakdown. In fact, there are probably numerous plant molecules that interact with the ECS without even realizing it because they haven’t been studied from this perspective. Flavonoids like kaempferol from fruits and vegetables may be able to inhibit an enzyme in the body known as FAAH18,  which could reduce breakdown of anandamide, and therefore provide a mood enhancing effect. And while not yet studied at any length, there are other plants and herbs that produce molecules that interfere with the breakdown of 2-AG, by inhibiting an enzyme known as MAGL.19 2-AG and the entourage effect Long before cannabis was being sold in legal dispensaries, in 1999 Israeli scientists looked at how certain lipids produced in the body may help to prevent the breakdown of 2-AG. These co-produced endocannabinoid-like lipids help to protect the endocannabinoid from enzymes that would attempt to metabolize them; somewhat similar to how an entourage would surround and protect their celebrity from swarming fans. This was the original description of the entourage effect before the term was later applied to whole plant cannabis. An interesting fact about 2-AG is that it was one of the first molecules to be associated with the “entourage effect”. Those Israli scientists, in that same paper in 1999,  made one of the earliest mentions of the modern definition of entourage effect that has been ascribed to cannabis saying that plant synergy “may play a role in the widely held (but not experimentally based) view that in some cases plants are better drugs than the natural products isolated from them.”20 Sources: Justinová Z, Yasar S, Redhi GH, Goldberg SR. The endogenous cannabinoid 2-arachidonoylglycerol is intravenously self-administered by squirrel monkeys. J Neurosci. 2011;31(19):7043-7048. doi:10.1523/JNEUROSCI.6058-10.2011 Mechoulam R, Ben-Shabat S, Hanus L, et al. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol. 1995;50(1):83-90. doi:10.1016/0006-2952(95)00109-d Baggelaar MP, Maccarrone M, van der Stelt M. 2-Arachidonoylglycerol: A signaling lipid with manifold actions in the brain. Prog Lipid Res. 2018;71:1-17. doi:10.1016/j.plipres.2018.05.002 Kirkham TC, Williams CM, Fezza F, Di Marzo V. Endocannabinoid levels in rat limbic forebrain and hypothalamus in relation to fasting, feeding and satiation: stimulation of eating by 2-arachidonoyl glycerol. Br J Pharmacol. 2002;136(4):550-557. doi:10.1038/sj.bjp.0704767 Izzo AA, Piscitelli F, Capasso R, et al. Peripheral endocannabinoid dysregulation in obesity: relation to intestinal motility and energy processing induced by food deprivation and re-feeding. Br J Pharmacol. 2009;158(2):451-461. doi:10.1111/j.1476-5381.2009.00183.x Nagarkatti P, Pandey R, Rieder SA, Hegde VL, Nagarkatti M. Cannabinoids as novel anti-inflammatory drugs. Future Med Chem. 2009;1(7):1333-1349. doi:10.4155/fmc.09.93 Baggelaar. 2-Arachidonoylglycerol. Prog Lipid Res. 2018;71:1-17 Turcotte C, Chouinard F, Lefebvre JS, Flamand N. Regulation of inflammation by cannabinoids, the endocannabinoids 2-arachidonoyl-glycerol and arachidonoyl-ethanolamide, and their metabolites. J Leukoc Biol. 2015;97(6):1049-1070. doi:10.1189/jlb.3RU0115-021R Imperatore R, Morello G, Luongo L, et al. Genetic deletion of monoacylglycerol lipase leads to impaired cannabinoid receptor CB₁R signaling and anxiety-like behavior. J Neurochem. 2015;135(4):799-813. doi:10.1111/jnc.13267 Baggelaar. 2-Arachidonoylglycerol. Prog Lipid Res. 2018;71:1-17 Silveira KM, Wegener G, Joca SRL. Targeting 2-arachidonoylglycerol signalling in the neurobiology and treatment of depression. Basic Clin Pharmacol Toxicol. 2021;129(1):3-14. doi:10.1111/bcpt.13595 Baggelaar. 2-Arachidonoylglycerol. Prog Lipid Res. 2018;71:1-17 Winters ND, Bedse G, Astafyev AA, et al. Targeting diacylglycerol lipase reduces alcohol consumption in preclinical models [published online ahead of print, 2021 Jul 22]. J Clin Invest. 2021;146861. doi:10.1172/JCI146861 Serrano A, Parsons LH. Endocannabinoid influence in drug reinforcement, dependence and addiction-related behaviors. Pharmacol Ther. 2011;132(3):215-241. doi:10.1016/j.pharmthera.2011.06.005 Baggelaar. 2-Arachidonoylglycerol. Prog Lipid Res. 2018;71:1-17 Ueda N, Tsuboi K. Discrimination between Two Endocannabinoids. Chemistry & Biology. 2012;19(5):545-547. doi:10.1016/j.chembiol.2012.05.001 Di Marzo V, Sepe N, De Petrocellis L, et al. Trick or treat from food endocannabinoids?. Nature. 1998;396(6712):636-637. doi:10.1038/25267 Thors L, Belghiti M, Fowler CJ. Inhibition of fatty acid amide hydrolase by kaempferol and related naturally occurring flavonoids. Br J Pharmacol. 2008;155(2):244-252. doi:10.1038/bjp.2008.237 Yang, R., Lu, Y., & Liu, J. (2014). Identification of tanshinone IIA as a natural monoacylglycerol lipase inhibitor by combined in silico and in vitro approach. MedChemComm, 5(10), 1528–1532. Mechoulam R, Ben-Shabat S. From gan-zi-gun-nu to anandamide and 2-arachidonoylglycerol: the ongoing story of cannabis. Nat Prod Rep. 1999;16(2):131-143. doi:10.1039/a703973e     This article was originally published on The Cannigma, and shared here with permission.

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How to fit CBD products into your alternative health regimen

How to fit CBD products into your alternative health regimen

Hemp and cannabis-derived medications may not be quite as mainstream as apple pie or multivitamins, but the days in which it was an almost completely illegal plant with little if any recognized medical benefits seem like a distant memory. Countless people now use CBD and other hemp-derived products as part of a prescribed medical regimen, as a daily health supplement, or just a go-to panacea to make the stress of daily life a little bit easier to manage.  Part of a natural, alternative lifestyle While many health conditions can be treated with more traditional pharmaceuticals, plant-based products may be a safer and healthier option – or at least a safe health supplement. For instance when it comes to pain relief, THC and CBD have shown to be safer than opioids; and for anti-anxiety and sleep aids, CBD does not appear to be habit-forming like benzodiazepines. These natural alternatives may also be effective as part of a daily “microdosing” regiment. This can mean taking a small amount of THC each day — for instance in the form of an edible — just to take the edge off and not to get intoxicated.  That doesn’t mean that CBD or other cannabis products should be seen as a cure all on their own. Rather, they should be considered part of a wider, holistic approach to healthy living, and the perfect accompaniment to other wellness steps, such as:  Getting a good night’s sleep  Staying up late and binging Netflix once you finally have some time to yourself is great fun, but it can come at a cost. Getting a good night’s sleep is a crucial step in leading a healthier lifestyle, and the benefits can be felt throughout the day.  The problem is, things often get in the way, and not just Netflix. Anxiety can make you restless, and before you know it you have to get up for work in three hours and you haven’t slept a wink.  With or without the potential anti-anxiety effects of CBD, making sure that you find a way to tune out the background noise and hit the sack at a reasonable hour can pay huge dividends when it comes to your health.  Meditation and mindfulness  Research has found that meditation can potentially have a variety of health benefits, including lowering blood pressure, reducing anxiety and depression, and may even provide some relief from conditions like irritable bowel syndrome and ulcerative colitis. Meditation can also help people focus themselves on the here and now, away from anxieties about the present and regrets of the past.  Many turn to cannabis for relaxation, alongside this natural therapy, though some people find that if they have consumed THC, the intoxicating effects can be too distracting when trying to meditate.  A healthy diet  What we put into our bodies is of crucial importance for our health. And this doesn’t mean just trying to steer away from tobacco or alcohol. It’s more about making sure you have a balanced diet that includes a wide range of fruits, vegetables, and grains, and doesn’t lean too heavily on carbs, sugar, and anything that’s deep fried and/or dusted in sugar.  That doesn’t mean you can’t cheat at times (or often, even), but making sure you eat right can make a huge difference in how you feel – even if you aren’t taking any supplements whatsoever.  Less screen time couldn’t hurt It’s nearly impossible to completely unplug these days, but if you spend every evening glued to your smartphone in bed, you’re going to have a harder time getting a good night’s sleep. The constant distractions, notifications, and social media outrages of the day can also boost your anxiety and stress, and make it much harder to just live in the moment. Reducing your screen time and finding a way to spend more time offline is a natural, drug-free way to boost your mental health. How CBD and cannabis products can help In recent years, cannabis has been the subject of a tremendous amount of scientific research, and in 2020 there was a record number of scientific studies published on cannabis.  While more human clinical trials are needed, the current evidence suggests there may be potential therapeutic benefits for the following ailments: Chronic pain —  the most common reason people turn to medical cannabis in the United States today. Both THC and CBD rich products may help those suffering from pain lasting several months.  Nausea and vomiting — cannabis has long been seen as a potential supportive treatment option for cancer patients undergoing chemotherapy. Cannabinoids may ease nausea and vomiting. Pharma has successfully isolated and recreated THC for chemotherapy-induced nausea and vomiting called Marinol, an FDA-approved drug available as a prescription.  Loss of sleep or insomnia — THC-rich cannabis products may help people fall asleep by addressing some of the underlying conditions, while the potential anti-anxiety effects of CBD helps people to shut out the noise and get some shut eye.  Inflammation — both THC and CBD have been shown to help reduce inflammation in conditions like multiple sclerosis, rheumatoid arthritis, and irritable bowel disease. It’s worth noting that folks may experience pain relief simply by taking the inflammation away. For people who are recommended to use cannabis by a medical professional, the regimen may likely include a stepwise approach in figuring out your sweet spot, or the lowest effective dose.  If you’re navigating this on your own, the best rule of thumb is to start low with the THC amount (around 2.5mg) and work your way up slowly until you find the dose that works best for you.  And it should go without saying that cannabis should not be used to replace prescription medication or potentially life-saving medication, and consumers should contact a healthcare  professional before making any decisions about their medication. How CBD and cannabis products work  It was only in the 1990s that researchers discovered the endocannabinoid system (ECS), a communication system which affects all types of functions in the body, from sleep to hunger to pain, to name just a few. The receptors of the system can be influenced by chemicals in cannabis known as cannabinoids — the two most well-known being THC and CBD.  By interacting with the receptors of the ECS, cannabis modulates the bodily functions that cause or exacerbate health conditions. Furthermore, some researchers believe that health conditions like migraines or fibromyalgia, among others, may actually be the result of endocannabinoid deficiencies.  Types of cannabis products  There is a truly bewildering variety of cannabis products today, but many of them fall under three categories: inhalation, oral, and topical.  Inhalation includes cannabis flowers that are smoked or vaped, or concentrated like shatter, wax, or oils that are vaporized and inhaled. This method is the most popular, and is very simple and straightforward, with an almost immediate onset.  Oral includes edibles like gummies or chocolates, as well as tinctures, beverages, or capsules. This method is preferred by those who don’t want to or can’t smoke or vape, but it is also an easy way to microdose or to stick to a set dosing regimen. The onset depends on the type of edible (typical gummies can take up to an hour, while nano emulsified beverages can work much quicker), but it can take more than an hour. In addition, edibles produce a very different sensation than other intake methods, which many consumers prefer.  Edibles like Dimer illustrate how this works. Dimer is a hemp-derived, full-spectrum edible that provides a generous serving of 75mg CBD, 6mg of THC, 1mg of CBG, and 5mg of CBC in every “calming caramel.”  Each individually wrapped piece can easily be portioned up for microdosing or times when you don’t want a whole piece. Keep in mind that this is not your average CBD product; 6mg of hemp-derived Delta-9 THC per serving can be a high dose for new consumers, or people that are usually sensitive to cannabis. Depending on your tolerance to THC, this can be a good accompaniment if you’d like to relax during your daily routine. Topicals include balms, savles, lotions, and patches, which are applied directly to the skin. Used to help with skin conditions like psoriasis or eczema, topicals can also help ease muscle aches and soreness, and may be a therapeutic alternative for relief  without the use of prescription medication. That said, because topicals don’t penetrate the skin deep enough to enter the bloodstream, they are best used for localized areas and can be a great add-on to the other form factors for that dose layering effect.  Why CBD and THC can work so well together  Edibles like Dimer that have a high CBD content along with the THC may actually enhance the effectiveness of both cannabinoids. The cannabis plant is thought to have  more than 140 cannabinoids, along with 150 plus terpenes that provide the aroma and flavor of plants. Isolated on their own, each of these cannabinoids and terpenes may have unique, therapeutic effects. But when taken together, these chemicals are thought to work greater in concert.  Scientists have dubbed this synergistic relationship “the entourage effect,” and this hypothesis is behind the drive for products that are full spectrum or whole spectrum. The rationale being that if these various chemicals work better together, then it makes more sense not to develop isolates for specific cannabinoids or terpenes, rather, products that include a whole symphony of natural compounds working together. Take for instance how CBD and THC interact. THC has shown to provide great relief for pain or nausea, but many people may find that THC by itself can be dysphoric. CBD counters the unpleasant  “high” caused by THC, and may even help people “come down” when they get too high. In addition, CBD may  potentially alleviate some of the adverse effects associated with  THC, such as paranoia or anxiety.   CBD is generally well-tolerated, but it is not without side effects. Some people may experience nausea, drowsiness, dizziness, or changes in appetite. Similar to the effects of CBD on the intoxication of THC, THC may even help counter some of the side-effects with CBD – suggesting that a whole plant product with multiple chemical constituents is better than the constituent alone. Tips on how to dose with hemp products  When trying out hemp products, seek out products that include a full list of the ingredients, as well as a certificate of authenticity and lab results that indicate the full makeup of the cannabinoids, terpenes, and the presence of any contaminants.  Furthermore, when starting any wellness regimen, it’s best to take things slow, especially if you are not under the guidance of a healthcare professional.  If you’re using edibles, find products that include a clear quantifier of CBD and/or THC (and other cannabinoids) per serving, and which can easily be parcelled up for smaller or larger doses. This will help you make sure you get a consistent dose each time, and should help stave off any surprises.  And while CBD hemp-derived products are generally considered safe (depending on the production methods), always err on the side of caution, especially if other medications or supplements are involved. If you are taking  prescription medications, be sure to talk to a healthcare professional to ensure there are no adverse interactions in combination.. Check that they don’t contain any allergens or other components that you cannot consume. Perhaps most importantly, listen to your body. While these products seem to work great for many people, if you are feeling any discomfort, dysphoria, or other adverse side effects like nausea, vomiting, or diarrhea, immediately consult with a healthcare professional who can advise you further.  View this post on Instagram A post shared by Savikalpa Academy (@savikalpa.academy)   This article was originally published on The Cannigma, and shared here with permission.

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How cannabis can treat inflammation

How cannabis can treat inflammation

Overview There is scientific evidence suggesting that cannabis can reduce inflammation and may be able to help treat conditions that are either caused by inflammation or have it as a key symptom, such as rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, and hepatitis. Still, some research suggests cannabis can also increase inflammation in certain circumstances.  The body’s endocannabinoid system plays a role in regulating inflammation responses — which is how cannabis is able to have inflammation modulating effects. Unfortunately, current research is lacking information on how to best utilize cannabis as a treatment for inflammation. Research on inflammation and cannabis Cannabis has been used for inflammation throughout the ages. As far back as the 1st century, Roman philosopher and commander Pliny the Elder recommended using cannabis for the inflammatory condition gout. In modern times, we know from animal studies that cannabis has strong anti-inflammatory properties, and many humans use cannabis to relieve symptoms of inflammatory conditions like rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, and hepatitis. In experimental models of rheumatoid arthritis (RA), cannabis’ anti-inflammatory effects have been shown to protect patients from the progression of the disease by reducing inflammation in the body. In one double-blind study on cannabis for RA patients, researchers found that cannabis not only relieved pain for these patients, it could also suppress the inflammatory activity of the disease.  Studies also show cannabis can help with multiple sclerosis (MS), in part by reducing inflammatory chemicals like cytokines produced in the body. In eight separate clinical studies, MS patients given cannabis reported improvement in symptoms and did better on objective measures like handwriting and bladder control tests.  Studies on inflammatory bowel diseases (IBD) like Crohn’s disease and colitis, have also shown some potential for treatment with cannabis. Animal studies show that cannabis’ active ingredients are capable of modulating the kind of inflammation in the GI tract that we see in IBD. Survey based studies on IBD have also found that cannabis can relieve its symptoms. Indeed, marijuana is an approved therapy for IBD in most jurisdictions where it is medically legal.  In human studies, including one placebo-controlled study, researchers have found that cannabis use was associated with improvement of disease activity in Crohn’s disease and reduction of other medications. Unfortunately, one study also found that cannabis use is associated with greater risk of requiring surgery for Crohn’s disease — which complicates our understanding of cannabis’ impact on this condition.  Cannabis may also help reduce viral infection related inflammation — in some cases also reducing the overall death rate. In animal studies, cannabis’ active chemical THC was able to protect mice from hepatitis, by reducing inflammatory responses. Some studies also showed it could help reduce risk of sepsis (a dangerous inflammatory response that can occur with infection) and even improved recovery rates for infections like malaria. But importantly, in other animal experiments, cannabis use decreased survival rates for influenza.  Other studies show cannabis’ inflammatory reductions may help reduce the growth of certain cancers that are triggered by chronic inflammation. CBD and inflammation Inflammatory relieving properties have also been found for CBD, a medicinal chemical found in cannabis which doesn’t cause the kind of psychotropic high we see with THC. For example, in animal models of rheumatoid arthritis, CBD stopped the progression of arthritis, while also relieving symptoms like pain.  There is also animal research suggesting that CBD can reduce inflammation in the gut Still, in one study, low dose CBD (unlike THC) did not show any impact on the progression or symptoms of Crohn’s disease.  That said, one review of the literature found that CBD could be a helpful treatment for inflammatory conditions, because it can stop or slow inflammatory factors like the production of cytokines.  Other studies looking at CBD’s effects on inflammation suggest that it may be particularly helpful for certain cardiovascular disorders, inflammatory bowel diseases, rheumatoid arthritis, types 1 and 2 diabetes, atherosclerosis, Alzheimer disease, hypertension, the metabolic syndrome, ischemia-reperfusion injury, depression, and neuropathic pain. How cannabis works on inflammation  The endocannabinoid system (ECS) exists in all vertebrates and helps regulate crucial functions such as sleep, pain, and appetite. The human body produces its own cannabinoids, which modulate and activate its various functions, but as its name suggests, the endocannabinoid system can also be modulated and activated by cannabinoids found in the cannabis plant. Because the entire system was only discovered in the past 30 years, scientists still have much to learn about the myriad ways cannabis affects the human body. When it comes to modulating inflammation, cannabinoids mainly work by stimulating the ECS’ primary receptors, CB1 and CB2, along with lesser known receptors associated with the system. Our bodies’ natural cannabinoids, like anandamide and 2-AG, play an important role in these inflammatory effects, signaling increases and decreases in inflammation via these receptors, but external cannabinoids from cannabis can also stimulate these functions. When cannabinoids stimulate the ECS receptors, they cause a number of anti-inflammatory effects, such as reducing cytokine and chemokine production (which are markers of inflammation), increasing T-regulatory cell activity (which suppress inflammatory responses).  Still it’s notable that while cannabinoids can reduce certain inflammatory factors, they can increase others, in some cases worsening inflammation. For example, in one study, levels of an anti-inflammatory cytokine decreased and a pro-inflammatory cytokine increased in response to THC. Some researchers say this suggests different types of cells may respond differently to cannabinoids when it comes to inflammation.  In addition, some research has indicated cannabinoids may impact inflammation through routes other than receptor stimulation as well. But more research is needed to fully understand these alternative mechanisms. Using cannabis for inflammation If you are using cannabis for the treatment of inflammation, the best first step is to talk to a doctor who specializes in cannabinoid medicine. Because inflammation is a symptom present in a variety of conditions that have different factors to consider, the best way to utilize cannabis for inflammation may differ with each condition. Your treatment should be tailored to your specific condition — rather than inflammation in general.  Still, the research is fairly limited when it comes to specifying how to best utilize cannabis for inflammation with any of these conditions. The research above includes studies using a few different methods for taking cannabis, including inhalation, oral ingestion, and rectal suppositories. Studies also show that cannabis can reduce inflammation when used topically. But there have yet to be comparisons on whether any methods outperform the others in terms of treating inflammation. Similarly, the studies above show cannabis’ main compounds, THC and CBD, are both able to reduce inflammation — separately or in combination with each other — but don’t tell us whether one or the other might be superior in creating these effects. Potential side effects of cannabis use Cannabis can also have side effects — particularly high-THC cannabis. These may include temporary psychoactive effects such as mental confusion, lightheadedness, euphoria, anxiety, and slower cognitive skills; or uncomfortable physiological changes like, coughing, allergies, dry mouth and eyes, increased appetite, heart palpitations, and drowsiness.  For inflammation treatment, it’s also important to note that while cannabis often reduces inflammation, some research has shown its ability to increase inflammation as well. In addition, there is a worry from some researchers that cannabis’ pain relieving properties might mask ongoing inflammation.   View this post on Instagram A post shared by Savikalpa Academy (@savikalpa.academy)     This article was originally published on The Cannigma, and shared here with permission.

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How cannabis affects your memory

How cannabis affects your memory

The main active chemical in cannabis, tetrahydrocannabinol (THC), may have a negative impact on short-term memory. Some research even points to memory issues and changes to the brain for longer-term cannabis users. Still, the data also suggests that using cannabidiol (CBD) can reverse or prevent these issues — and that both CBD and THC may have big potential benefits for those suffering from Alzheimer’s disease.  Cannabis has a wide range of medicinal and wellness-enhancing benefits, but many worry about its possible impact on memory. These worries are not unfounded, the research suggests, but the picture isn’t entirely negative either. How cannabis interacts with memory To understand how cannabis interacts with memory, we first need to understand how cannabis interacts with the body as a whole — through the endocannabinoid system. This system, found in humans as well as all other vertebrates, is always at work in the body but also interacts with cannabinoids found in the cannabis plant. The endocannabinoid system as a whole is tasked with maintaining homeostasis or balance in the human body. To do this, it regulates a number of bodily functions such as sleep, hunger, energy, temperature, pain, and immune function. Importantly, it also helps to regulate our processes surrounding memory and learning.  There is strong evidence that the endocannabinoid system is involved in regulating memory, and in particular, that the cannabinoid receptor CB1 is important to this process. Both animal and human studies have found that activating CB1 with the endocannabinoid anandamide — as well as THC and synthetic versions of THC — can cause deficits in short-term memory.  In animal studies, both rodents and squirrel monkeys performed worse on spatial learning tasks when CB1 was activated. Researchers were able to reverse this effect with the drug rimonabant, which deactivates CB1 activity, adding further evidence that CB1 is involved. Some researchers have hypothesized that this effect is due to the high density of CB1 receptors in the hippocampus, which is also involved in memory tasks.  The benefits of marijuana for memory When it comes to cannabis’s effect on memory, the evidence suggests it may be detrimental or beneficial depending on a number of factors. On the beneficial side, there is a growing body of evidence pointing towards cannabis as a potential treatment for Alzheimer’s Disease.   In the study of Alzheimer’s, one of the primary hallmarks of the disease is the accumulation of toxic beta-amyloid plaques, which build up in the brain outside of neurons. This kills off neurons, leading to severe cognitive impairment and problems with memory. But research suggests that cannabis, particularly its active cannabinoids THC and CBD, may be able to help slow the progression of Alzheimer’s Disease by reducing the levels of beta-amyloid in the brain, as well as improving other important factors related to the disease.  In one study, for example, researchers found that THC is able to lower levels of beta-amyloid in the brain and prevent it from accumulating in the brain, by interacting with beta-amyloid peptides. It was also able to reduce GSK-3 (another important marker for Alzheimer’s Disease), and enhance mitochondria function, which is dysfunctional in Alzheimer’s Disease.  A small human study on 11 patients using THC to treat the symptoms of Alzheimer’s disease found that it was safe and well tolerated. Patients who used it for four weeks had significant reductions in delusions related to the condition, as well as improvement in aggression, irritability, apathy, sleep, and caregiver distress.  Synthetic THC hasn’t been shown to perform as well, however. Two trials using synthetic THC found that while it was safe and well-tolerated, it did not offer patients any significant therapeutic effect.  Studies looking at CBD have also found positive results. A review of existing research including human, animal, and lab studies found that CBD protected cells from beta-amyloid toxicity, increased cell survival, and encouraged new neuron growth in the hippocampus — as well as improving other factors involved with Alzheimer’s Disease. The researchers also found that when THC and CBD are used together, the effect is even more substantial, suggesting this combined cannabinoid treatment should be investigated further.  But marijuana is more than just THC and CBD. Other molecules found in cannabis, such as terpenes, also show potential as treatment for dementia. Most notably, pinene, limonene, and beta-caryophyllene (BCP) all seem to interact with beta-amyloids, although all of the research has been conducted either in labs or on animals. Pinene has also been shown to reduce some of the negative effects THC has on memory. One study suggested a “possible neuroprotective potential of alpha pinene for the management of dementia with learning and memory loss.” The authors of another study wrote that “high levels of limonene in food or medication are expected to help treat or prevent Alzheimer’s disease.” Beta-caryophyllene, given orally in a study on mice, was shown to prevent cognitive impairment. The evidence is preliminary and based entirely on animal models, yet terpenes may explain the varying cognitive effects of different cannabis varieties.   Is marijuana bad for memory? While cannabis may have benefits for those with Alzheimer’s, other research points to potential detrimental effects of cannabis on memory. For one thing, cannabis is known to produce mild, short-term memory impairment for some who are actively high on the drug. Still, it’s not entirely clear that these effects occur in all cannabis users. For example, in a survey of 1,333 British cannabis users, only a small subset (6.1%) reported impaired memory.  These changes are usually reversed sometime after the cannabis high subsides, although there is some disagreement as to how long. Some report that these effects subside after the high is gone, while others say it may linger. A small study on cannabis-dependent adolescents found that the cannabis-using subjects had short-term memory deficits that lasted for six weeks after the last use of cannabis. Still, with such a smaller sample size, more research is needed to confirm these results. A much larger review of 69 studies found no evidence for cognitive deficits after 72 hours of cannabis abstinence.  Still, other studies have found that long-term or heavy cannabis use may also lead to problems with working memory and verbal episodic memory, with impairments in encoding, storing and retrieving memories. And some alterations have been found in brain structure and function for cannabis users, specifically in the areas of the brain that support memory processing.  Some studies have found that cannabis users had higher activation in spatial memory related areas of the brain. Researchers hypothesized that they were ‘working harder’ to compensate for the changes to the brain caused by cannabis.  Interestingly, some research suggests that CBD may alleviate the memory problems induced by the THC in cannabis. Comparing cannabis users who used high-THC cannabis to those who used the same amount of THC alongside high amounts of CBD, one study found that the second group did not have memory impairment. This suggests CBD may have a protective effect for memory — essentially shielding it from the impacts of THC. For those who are concerned about cannabis’ negative effects on memory, one might consider utilizing whole plant extracts with a balanced THC:CBD profile and other cannabinoids and terpenes like cannabichromene (CBC), cannabigerol (CBG), limonene, pinene, and beta-caryophyllene.   This article was originally published on The Cannigma, and shared here with permission.

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